<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03268954</url>
  </required_header>
  <id_info>
    <org_study_id>Pevonedistat-3001</org_study_id>
    <secondary_id>2017-000318-40</secondary_id>
    <secondary_id>U1111-1189-8055</secondary_id>
    <secondary_id>MOH_2018-02-04_002154</secondary_id>
    <secondary_id>JapicCTI-183848</secondary_id>
    <secondary_id>NCI-2017-02059</secondary_id>
    <nct_id>NCT03268954</nct_id>
  </id_info>
  <brief_title>Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)</brief_title>
  <acronym>PANTHER</acronym>
  <official_title>A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda Development Center Americas, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether the combination of pevonedistat and&#xD;
      azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine.&#xD;
      (An event is defined as death or transformation to AML in participants with MDS or CMML,&#xD;
      whichever occurs first, and is defined as death in participants with low-blast AML).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to&#xD;
      treat people with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic&#xD;
      leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment&#xD;
      with azacitidine. This study will look at the overall survival, event-free survival and&#xD;
      response to treatment in people who take pevonedistat and azacitidine when compared to people&#xD;
      who take single-agent azacitidine.&#xD;
&#xD;
      The study will enroll approximately 450 participants. Once enrolled, participants will be&#xD;
      randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment&#xD;
      groups in 28-day treatment cycles:&#xD;
&#xD;
        -  Pevonedistat 20 mg/m^2 and azacitidine 75 mg/m^2 combination&#xD;
&#xD;
        -  Single-agent azacitidine 75 mg/m^2&#xD;
&#xD;
      All participants will receive azacitidine via intravenous or subcutaneous route. Participants&#xD;
      randomized to the combination arm will also receive pevonedistat intravenous infusion.&#xD;
&#xD;
      This multi-center trial will be conducted Spain, Belgium, Brazil, Canada, Czech Republic,&#xD;
      France, Germany, Israel, Italy, the United States, Australia, Greece, Japan, Mexico, Poland,&#xD;
      Russia, Korea, Turkey, China and United Kingdom. The overall time to participate in this&#xD;
      study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days&#xD;
      after the last dose of study drug or before the start of subsequent anti-neoplastic therapy&#xD;
      if that occurs sooner.&#xD;
&#xD;
      Participants with HR MDS or CMML will have EFS follow-up study visits every month if their&#xD;
      disease has not transformed to AML and they have not started subsequent therapy. Participants&#xD;
      with low-blast AML will have response follow-up study visits every month until they relapse&#xD;
      from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted&#xD;
      every 3 months) when they have confirmed transformation to AML (for participants with HR MDS&#xD;
      or CMML at enrollment) or experienced PD (for participants with low-blast AML at study&#xD;
      enrollment).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Anticipated">December 29, 2023</completion_date>
  <primary_completion_date type="Actual">May 28, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event-Free Survival (EFS)</measure>
    <time_frame>From randomization until transformation to acute myeloid leukemia, or death due to any cause up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization [WHO] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Overall survival was defined as the time from randomization to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan-Meier Estimates of Six-Month Survival Rate</measure>
    <time_frame>Up to Month 6</time_frame>
    <description>Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan-Meier Estimates of One-Year Survival Rate</measure>
    <time_frame>Up to Year 1</time_frame>
    <description>Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30</measure>
    <time_frame>Up to Day 30</time_frame>
    <description>30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60</measure>
    <time_frame>Up to Day 60</time_frame>
    <description>60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants</measure>
    <time_frame>From randomization until transformation to AML till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)</measure>
    <time_frame>From randomization until CR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 gram per deciliter (g/dL) hemoglobin (Hgb),&gt;=100*10^9/liter (/L) platelets (pl),&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With CR and Marrow CR</measure>
    <time_frame>From randomization until CR or marrow CR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and &gt;=11 g/dL Hgb, &gt;=100*10^9/L platelets (pl), &gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)</measure>
    <time_frame>From randomization until, CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%. HI: Hgb increase &gt;=1.5 g/dL if &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline&gt;20*10^9/L or increase from &lt;20*10^9/L to &gt;20*10^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With CR and Marrow CR and PR</measure>
    <time_frame>From randomization until CR or Marrow CR and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)</measure>
    <time_frame>From randomization until CR, marrow CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still&gt;5%. HI: Hgb increase &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline&gt;20*10^9/L or increases from &lt;20*10^9/L to &gt;20*10^9/L and by at least 100%; neutrophil increases by 100% and absolute increases of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Overall Response (OR)</measure>
    <time_frame>From randomization until CR and PR or CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR or PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still&gt;5%. For low-blast AML-CR:morphologic leukemia-free state&gt;1.0*10^9 neutrophils, &gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but &gt;=50% decrease in bone marrow aspirate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Overall Response 2 (OR2)</measure>
    <time_frame>From randomization until, CR, PR or HI or CR, CRi or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>OR2=participant with best overall response of CR+PR+HI in HR MDS/CMML participants,or of CR+CRi+PR in low-blast AML participants.CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still &gt;5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)&lt;11 g/dL;pl inc≥30*10^9/L if BL&gt;20*10^9/L or inc from &lt;20*10^9/L to &gt;20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of &gt;0.5*10^9/L if BL&lt;100*10^9/L.For low-blast AML-CR:morphologic leukemia-free state &gt;1.0*10^9 neutrophils,≥100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl&lt;100*10^9/L;PR:all CR hematological values but ≥50% decrease in BM aspirate.Number of responders determined by independent review committee(IRC) assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Complete Remission (CR)</measure>
    <time_frame>From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)</measure>
    <time_frame>From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). Disease responses for low-blast AML were based on the Revised IWG Response Criteria for AML. CR is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 g/dL hemoglobin (Hgb),&gt;=100*10^9/liter (/L) platelets (pl),&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Overall Response (OR)</measure>
    <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR+PR for HR MDS/CMML and CR+Cri+ PR for low-blast AML.CR for HR MDS/CMML:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR:all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still &gt;5%. For low-blast AML-CR: morphologic leukemia-free state &gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with CRi: fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but &gt;=50% decrease in % of blasts in bone marrow aspirate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Overall Response 2 (OR2)</measure>
    <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Duration of OR2: from date of first documentation of CR+PR+HI to first documentation of PD/relapse after CR/PR for responders of CR+PR+HI for HR MDS/CMML and CR,CRi,PR for low-blast AML. For HR MDS/CMML-CR:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb, &gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment, still &gt;5%; HI:Hgb inc &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl inc&gt;=30*10^9/L if baseline&gt;20*10^9/L or inc from&lt;20*10^9/L to&gt;20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.For low-blast AML-CR: morphologic leukemia-free state,&gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi: fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl &lt;100*10^9/L;PR:all CR hematological values but&gt;=50% decrease in bone marrow aspirate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence</measure>
    <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence</measure>
    <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Duration of RBC and platelet transfusion independence was defined as the longest time between the last RBC and/or platelet transfusion before the start of the RBC and/or platelet transfusion-independent period and the first RBC and/or platelet transfusion after the start of the transfusion-independent period, which occurs &gt;= 8 weeks later.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)</measure>
    <time_frame>From randomization until CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Time to first CR or PR is defined as the time from randomization to first documented CR or PR, whichever occurs first. Disease responses for HR MDS or CMML or low-blast AML cycle 6 are based on Modified IWG Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. For HR MDS or CMML-CR:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still&gt;5%; For low-blast AML-CR: morphologic leukemia-free state,&gt;1.0*10^9/L neutrophils, pl&gt;=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Hematologic Improvement (HI)</measure>
    <time_frame>From randomization until HI till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline &gt;20*10^9/L or increase from &lt;20*10^9/L to &gt;20*10^9/L by at least 100%; neutrophil increase by 100% and absolute increase of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML</measure>
    <time_frame>From randomization until transformation to AML or until initiation of subsequent therapy till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Inpatient hospital admission data was collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurred first. Transformation to AML is defined, according to WHO Classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progressive Disease (PD), Relapse After CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death</measure>
    <time_frame>From randomization until PD, relapse after CR, or relapse after CR or PR, or death due to any cause, whichever occurs first till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Time to PD, relapse after CR(low-blast AML), relapse after CR or PR(HR MDS/CMML), or death,defined as time from date of randomization until date of first documentation of PD,relapse after CR(low-blast AML),relapse after CR or PR(HR MDS/CMML),or death due to any cause, whichever occurs first. In HR MDS/CMML,PD: Participants with&lt;5% blasts:&gt;=50% inc &gt;5% blasts, with 5%-9% blasts:&gt;=50% inc&gt;10% blasts, with 10%-19% blasts:&gt;=50% inc &gt;20% blasts,with 20%-30% blasts, at least 50% decrement from maximum remission/response in granulocytes or pl or reduction in Hgb by&gt;=2 g/dL/new transfusion dependence.Relapse after CR or PR: return to pretreatment bone marrow blast %/Decrement of &gt;=50% from maximum remission/response levels in granulocytes/pl/reduction in Hgb conc.&gt;=1.5 g/dL/transfusion dependence. In AML,PD:&gt;50% inc in bone marrow blasts to &gt;30% blasts,&gt;50% inc in circulating blasts to&gt;30% blasts in peripheral blood, Development of extramedullary disease/new sites of extramedullary leukemia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30</measure>
    <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The percentage of participants for each parameter score were categorized as improved, stable, and worsened. Only categories with at least one participant with event are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Pevonedistat</measure>
    <time_frame>Cycle 1 Day 1 predose and multiple time points (up to 4 hours) post dose; Cycle 1 Days 3 and 5 predose; Cycle 2 and 4 Day 1 at multiple time points (up to 3 hours) post dose; Cycle 4 Day 3 predose (Cycle length= 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Overall Response in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</measure>
    <time_frame>From randomization until CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR + PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still&gt;5%. For low-blast AML-CR: morphologic leukemia-free state, &gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl&lt;100*10^9/L; PR: all CR hematological values but&gt;=50% decrease in the percentage of blasts to 5% to 25% in bone marrow aspirate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-Free Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</measure>
    <time_frame>From randomization until transformation to AML if eligible or death till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>Event was defined as death or transformation to AML in participants with MDS or CMML, whichever occurred first. Transformation to AML was defined, according to World Health Organization (WHO) Classification as a participant having &gt;20% blasts in the blood or marrow and increase of blast count by 50%. Event was defined as death in participants with low-blast AML.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</measure>
    <time_frame>From randomization until death till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
    <description>OS was calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored as of the date the participant was last known to be alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Overall Response by Cycle 6</measure>
    <time_frame>Up to Cycle 6 (up to approximately Day 168)</time_frame>
    <description>Responses for HR MDS/CMML are based on Modified International Working Group (IWG) Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR and PR for HR MDS/CMML and CR+CR with incomplete blood count recovery(CRi)+PR for low-blast AML. CR for HR MDS/CMML:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11g/dL hemoglobin (Hgb),&gt;=100*10^9/L platelet (pl),&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood, and PR:all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%. For low-blast AML-CR:morphologic leukemia-free state,&gt;1.0*10^9 neutrophils, &gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L/thrombocytopenia (pl&lt;100*10^9/L); PR:all CR hematological values but&gt;=50% decrease in percentage of blasts to 5%-25% in bone marrow aspirate.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">454</enrollment>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Leukemia, Myelomonocytic, Chronic</condition>
  <condition>Leukemia, Myeloid, Acute</condition>
  <arm_group>
    <arm_group_label>Azacitidine 75 mg/m^2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azacitidine 75 milligram per square meter (mg/m^2) intravenous (IV) or subcutaneous (SC) injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>Azacitidine intravenous or subcutaneous formulation.</description>
    <arm_group_label>Azacitidine 75 mg/m^2</arm_group_label>
    <arm_group_label>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pevonedistat</intervention_name>
    <description>Pevonedistat intravenous infusion.</description>
    <arm_group_label>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML&#xD;
             (i.e., with white blood cell [WBC] &lt;13,000/microliter [mcL]) or low-blast acute&#xD;
             myelogenous leukemia (AML).&#xD;
&#xD;
          2. Has MDS or CMML and must also have one of the following Prognostic Risk Categories,&#xD;
             based on the Revised International Prognostic Scoring System (IPSS-R):&#xD;
&#xD;
               -  Very high (&gt;6 points).&#xD;
&#xD;
               -  High (&gt;4.5-6 points).&#xD;
&#xD;
               -  Intermediate (&gt;3-4.5 points): a participant determined to be in the Intermediate&#xD;
                  Prognostic Risk Category is only allowable in the setting of &gt;=5% bone marrow&#xD;
                  myeloblasts.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.&#xD;
&#xD;
          4. Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM)&#xD;
             score &gt;=4 for intensive, induction chemotherapy as calculated using the simplified&#xD;
             model described by Walter and coworkers.&#xD;
&#xD;
        Calculation of TRM score:&#xD;
&#xD;
          -  0 for (age &lt;61 years), +2 for (age 61-70 years), +4 for (age &gt;=71 years).&#xD;
&#xD;
          -  + 0 for (PS=0), +2 for (PS=1), +4 for (PS &gt;1).&#xD;
&#xD;
          -  + 0 for (platelets &lt;50), +1 for (platelets &gt;=50).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other&#xD;
             antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or&#xD;
             azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide,&#xD;
             except that lenalidomide may not be given within 8 weeks before the first dose of&#xD;
             study drug.&#xD;
&#xD;
          2. Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone&#xD;
             marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or&#xD;
             bone marrow, or by other accepted analysis.&#xD;
&#xD;
          3. Participants with AML with a WBC count &gt;50,000/mcL. Participants who are cytoreduced&#xD;
             with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility&#xD;
             criteria.&#xD;
&#xD;
          4. Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation.&#xD;
             The reason a participant is not eligible for intensive chemotherapy and/or allogeneic&#xD;
             stem cell transplantation may consist of one or more of the following factors:&#xD;
&#xD;
               -  Age &gt;75.&#xD;
&#xD;
               -  Comorbidities.&#xD;
&#xD;
               -  Inability to tolerate intensive chemotherapy (e.g., participants with AML with&#xD;
                  20%-30% blasts and TRM &gt;=4).&#xD;
&#xD;
               -  Physician decision (e.g., lack of available stem cell donor).&#xD;
&#xD;
               -  The reason a participant is not eligible should be documented in the electronic&#xD;
                  case report form (eCRF).&#xD;
&#xD;
          5. Has either clinical evidence of or history of central nervous system involvement by&#xD;
             AML.&#xD;
&#xD;
          6. Has active uncontrolled infection or severe infectious disease, such as severe&#xD;
             pneumonia, meningitis, or septicemia.&#xD;
&#xD;
          7. Is diagnosed or treated for another malignancy within 2 years before randomization or&#xD;
             previously diagnosed with another malignancy and have any evidence of residual&#xD;
             disease.&#xD;
&#xD;
          8. Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they&#xD;
             have undergone resection.&#xD;
&#xD;
          9. Has prothrombin time (PT) or aPTT &gt;1.5× upper limit of normal (ULN) or active&#xD;
             uncontrolled coagulopathy or bleeding disorder. Participants therapeutically&#xD;
             anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors,&#xD;
             or heparin are excluded from enrollment.&#xD;
&#xD;
         10. Has known human immunodeficiency virus (HIV) seropositive.&#xD;
&#xD;
         11. Has known hepatitis B surface antigen seropositive, or known or suspected active&#xD;
             hepatitis C infection. Note: Participants who have isolated positive hepatitis B core&#xD;
             antibody (i.e., in the setting of negative hepatitis B surface antigen and negative&#xD;
             hepatitis B surface antibody) must have an undetectable hepatitis B viral load.&#xD;
&#xD;
         12. Has known hepatic cirrhosis or severe preexisting hepatic impairment.&#xD;
&#xD;
         13. Has known cardiopulmonary disease defined as unstable angina, clinically significant&#xD;
             arrhythmia, congestive heart failure (New York Heart Association Class III or IV),&#xD;
             and/or myocardial infarction within 6 months before first dose, or severe pulmonary&#xD;
             hypertension.&#xD;
&#xD;
         14. Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the&#xD;
             first dose of pevonedistat.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Southern Cancer Center - USOR</name>
      <address>
        <city>Daphne</city>
        <state>Alabama</state>
        <zip>36526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Cancer Center - USOR</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Cancer Center - USOR</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Cancer Center- USOR</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Regional Medical Center - CTCA - PPDS</name>
      <address>
        <city>Goodyear</city>
        <state>Arizona</state>
        <zip>85338</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates (Orange HOPE) - USOR</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates (Rudasill HOPE) - USOR</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates (Wilmot HOPE) - USOR</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc</name>
      <address>
        <city>Corona</city>
        <state>California</state>
        <zip>92879</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Cancer Care Medical Group Inc</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emad Ibrahim, MD, Inc</name>
      <address>
        <city>Redlands</city>
        <state>California</state>
        <zip>92373</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Aurora) - USOR</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Boulder) - USOR</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Colorado Springs) - USOR</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Quest Diagnostics, INC</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute - PPDS</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presbyterian Saint Lukes Medical Center Laboratory</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presbyterian/St. Luke's Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Williams) - USOR</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Denver) - USOR</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Foundation Health Plan</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laboratory Corporation of America</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Lakewood) - USOR</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Littleton) - USOR</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Lone Tree) - USOR</name>
      <address>
        <city>Lone Tree</city>
        <state>Colorado</state>
        <zip>80124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Longmont) - USOR</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Parker) - USOR</name>
      <address>
        <city>Parker</city>
        <state>Colorado</state>
        <zip>80138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Pueblo) - USOR</name>
      <address>
        <city>Pueblo</city>
        <state>Colorado</state>
        <zip>81008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers (Thornton) - USOR</name>
      <address>
        <city>Thornton</city>
        <state>Colorado</state>
        <zip>80260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medstar Research Institute</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Altamonte Springs</city>
        <state>Florida</state>
        <zip>32701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Bonita Springs</city>
        <state>Florida</state>
        <zip>34135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Brandon</city>
        <state>Florida</state>
        <zip>33511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Cape Coral</city>
        <state>Florida</state>
        <zip>33914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33761</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Jacksonville - PPDS</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Largo</city>
        <state>Florida</state>
        <zip>33770</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Lecanto</city>
        <state>Florida</state>
        <zip>34461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Health System (N Kendall) - USOR</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Naples</city>
        <state>Florida</state>
        <zip>34102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>New Port Richey</city>
        <state>Florida</state>
        <zip>34655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34471</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <zip>33980</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Spring Hill</city>
        <state>Florida</state>
        <zip>34608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Tavares</city>
        <state>Florida</state>
        <zip>32778</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>The Villages</city>
        <state>Florida</state>
        <zip>32159</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Venice</city>
        <state>Florida</state>
        <zip>34285</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Florida Cancer Specialists South</name>
      <address>
        <city>Venice</city>
        <state>Florida</state>
        <zip>34292</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Florida</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - NORTH - SCRI - PPDS</name>
      <address>
        <city>Winter Park</city>
        <state>Florida</state>
        <zip>32792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute, Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Regional Medical Center</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Caldwell Cancer Care Center</name>
      <address>
        <city>Caldwell</city>
        <state>Idaho</state>
        <zip>83605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Medical Center</name>
      <address>
        <city>Nampa</city>
        <state>Idaho</state>
        <zip>83687</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Menorah Medical Center</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centerpoint Medical Center</name>
      <address>
        <city>Independence</city>
        <state>Missouri</state>
        <zip>64057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCA Midwest Health - SCRI - PPDS</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Cancer Specialists</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Jersey Hematology Oncology Associates LLC</name>
      <address>
        <city>Brick</city>
        <state>New Jersey</state>
        <zip>08724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Theurer Cancer Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Jersey Hematology and Oncology</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical Center - Monitoring Location</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Strong Memorial Hospital</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care, Inc.</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care, Inc.</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care Inc - USOR</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care Inc - USOR</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care, Inc - Fairfield</name>
      <address>
        <city>Fairfield</city>
        <state>Ohio</state>
        <zip>45014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillcrest Hospital Cancer Care Center</name>
      <address>
        <city>Mayfield</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Hospital</name>
      <address>
        <city>Bethlehem</city>
        <state>Pennsylvania</state>
        <zip>18015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's University Health Network</name>
      <address>
        <city>Easton</city>
        <state>Pennsylvania</state>
        <zip>18045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <zip>29640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System Cancer Institute</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Seneca</city>
        <state>South Carolina</state>
        <zip>29672</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Health System</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - DICKSON - SCRI - PPDS</name>
      <address>
        <city>Dickson</city>
        <state>Tennessee</state>
        <zip>37055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - FRANKLIN - SCRI - PPDS</name>
      <address>
        <city>Franklin</city>
        <state>Tennessee</state>
        <zip>37067</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - GALLATIN - SCRI - PPDS</name>
      <address>
        <city>Gallatin</city>
        <state>Tennessee</state>
        <zip>37066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - SUMMIT - SCRI - PPDS</name>
      <address>
        <city>Hermitage</city>
        <state>Tennessee</state>
        <zip>37076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - LEBANON - SCRI - PPDS</name>
      <address>
        <city>Lebanon</city>
        <state>Tennessee</state>
        <zip>37090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - MURFREESBORO - SCRI - PPDS</name>
      <address>
        <city>Murfreesboro</city>
        <state>Tennessee</state>
        <zip>37129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Center for Blood Centers - SCRI - PPDS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncolgy - BAPTIST - SCRI - PPDS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology NASH - SCRI - PPDS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - ST THOMAS WEST - SCRI - PPDS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology SKYLINE - SCRI - PPDS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - SOUTHERN HILLS - SCRI - PPDS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - SHELBYVILLE - SCRI - PPDS</name>
      <address>
        <city>Shelbyville</city>
        <state>Tennessee</state>
        <zip>37160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology - SMYRNA - SCRI - PPDS</name>
      <address>
        <city>Smyrna</city>
        <state>Tennessee</state>
        <zip>37167</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (West 38) - USOR</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (Balcones) - USOR</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (James Casey) - USOR</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78745</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (Medical City) - USOR</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (Tyler) - USOR</name>
      <address>
        <city>Longview</city>
        <state>Texas</state>
        <zip>75601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (E Common) - USOR</name>
      <address>
        <city>New Braunfels</city>
        <state>Texas</state>
        <zip>78130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (Round Rock) - USOR</name>
      <address>
        <city>Round Rock</city>
        <state>Texas</state>
        <zip>78681</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - San Antonio Medical Center - USOR</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology (Tyler) - USOR</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology and Hematology Associates of Southwest Virginia (Blacksburg) - USOR</name>
      <address>
        <city>Blacksburg</city>
        <state>Virginia</state>
        <zip>24060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology and Hematology Associates of Southwest Virginia (Low Moor) - USOR</name>
      <address>
        <city>Low Moor</city>
        <state>Virginia</state>
        <zip>24457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology and Hematology Associates of Southwest Virginia (Roanoke) - USOR</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology and Hematology Associates of Southwest Virginia Inc</name>
      <address>
        <city>Salem</city>
        <state>Virginia</state>
        <zip>24153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology and Hematology Associates of Southwest Virginia</name>
      <address>
        <city>Wytheville</city>
        <state>Virginia</state>
        <zip>24382</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icon Cancer Care Wesley</name>
      <address>
        <city>Auchenflower</city>
        <state>Queensland</state>
        <zip>4066</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icon Cancer Care Chermside</name>
      <address>
        <city>Chermside</city>
        <state>Queensland</state>
        <zip>4032</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icon Cancer Care South Brisbane</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icon Cancer Care</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icon Cancer Care Southport</name>
      <address>
        <city>Southport</city>
        <state>Queensland</state>
        <zip>4215</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <zip>1871</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Algemeen Ziekenhuis Klina</name>
      <address>
        <city>Brasschaat</city>
        <state>Antwerpen</state>
        <zip>2930</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU UCL Namur asbl - Site Godinne</name>
      <address>
        <city>Yvoir</city>
        <state>Namur</state>
        <zip>5530</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Jan AV</name>
      <address>
        <city>Brugge</city>
        <state>West-Vlaanderen</state>
        <zip>8000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner</name>
      <address>
        <city>Curitiba</city>
        <state>Parana</state>
        <zip>81520-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liga Norte Riograndense Contra O Cancer</name>
      <address>
        <city>Natal</city>
        <state>Rio Grande Do Norte</state>
        <zip>59075-740</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Pesquisas Oncologicas</name>
      <address>
        <city>Florianopolis</city>
        <state>Santa Catarina</state>
        <zip>88034-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre (HCPA) - PPDS</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidade Federal do Rio de Janeiro - UFRJ</name>
      <address>
        <city>Rio De Janeiro</city>
        <zip>21941-913</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Marcelina</name>
      <address>
        <city>Sao Paulo</city>
        <zip>08270-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Marcelina</name>
      <address>
        <city>Sao Paulo</city>
        <zip>08270-270</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaye Edmonton Clinic</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G1Z1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John Regional Hospital</name>
      <address>
        <city>Saint John</city>
        <state>New Brunswick</state>
        <zip>E2L 4L2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xuanwu Hospital Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100053</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Hradec Kralove</name>
      <address>
        <city>Hradec Kralove</city>
        <state>Kralovehradeck Kraj</state>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vseobecna Fakultni Nemocnice V Praze</name>
      <address>
        <city>Prague</city>
        <zip>128 08</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Kralovske Vinohrady</name>
      <address>
        <city>Praha</city>
        <zip>100 34</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cote de Nacre</name>
      <address>
        <city>Caen</city>
        <state>Calvados</state>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Le Mans</name>
      <address>
        <city>Le Mans</city>
        <zip>74000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Louis</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Tubingen</name>
      <address>
        <city>Tubingen</city>
        <state>Baden-Wurttemberg</state>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Leipzig</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>4103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Carl Gustav Carus an der TU Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>1307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marien Hospital Akademisches Lehrkrankenhaus</name>
      <address>
        <city>Dusseldorf</city>
        <zip>40479</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laiko General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Athens General Hospital 'G Gennimatas'</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Attikon University General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>12462</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Alexandroupolis</name>
      <address>
        <city>Alexandroupolis</city>
        <zip>68100</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laiko General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Ioannina</name>
      <address>
        <city>Ioannina</city>
        <zip>45500</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Larissa</name>
      <address>
        <city>Larissa</city>
        <zip>41110</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Patras</name>
      <address>
        <city>Patras</city>
        <zip>26504</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgios Papanikolaou General Hospital of Thessaloniki</name>
      <address>
        <city>Thessaloniki</city>
        <zip>57010</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edith Wolfson Medical Center</name>
      <address>
        <city>Holon</city>
        <zip>58100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <zip>91031</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center PPDS -</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galilee Medical Center</name>
      <address>
        <city>Nahariya</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZIV Medical Center</name>
      <address>
        <city>Safed</city>
        <zip>13100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Center PPDS</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN</name>
      <address>
        <city>Brescia</city>
        <state>Lombardia</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Centro Di Riferimento Oncologico Della Basilicata</name>
      <address>
        <city>Rionero in Vulture</city>
        <zip>85028</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital</name>
      <address>
        <city>Fukuyama</city>
        <state>Hirosima</state>
        <zip>720-0001</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokkaido University Hospital</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>060 8638</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fukushima Medical University Hospital</name>
      <address>
        <city>Fukushima-shi</city>
        <state>Hukusima</state>
        <zip>960-1295</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe City Medical Center General Hospital</name>
      <address>
        <city>Kobe-City</city>
        <state>Hyogo</state>
        <zip>650-0047</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital, Kyoto Prefectural University of Medicine</name>
      <address>
        <city>Kyoto-shi</city>
        <state>Kyoto</state>
        <zip>602-8566</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osakasayama</city>
        <state>Osaka</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Medical Center</name>
      <address>
        <city>Kawagoe</city>
        <state>Saitama</state>
        <zip>3508550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juntendo University Hospital</name>
      <address>
        <city>Bunkyo</city>
        <state>Tokyo</state>
        <zip>113-8431</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NTT Medical Center Tokyo</name>
      <address>
        <city>Shinagawa-ku</city>
        <state>Tokyo</state>
        <zip>141-8625</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyushu University Hospital</name>
      <address>
        <city>Fukuoka-city</city>
        <zip>812-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dokkyo Medical University Hospital</name>
      <address>
        <city>Mibu</city>
        <zip>321-0293</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nagasaki University Hospital</name>
      <address>
        <city>Nagasaki</city>
        <zip>8528102</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka Metropolitan University Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>545-8586</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yokohama City University Hospital</name>
      <address>
        <city>Yokohama-shi</city>
        <zip>232-0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Fukui Hospital</name>
      <address>
        <city>Yoshida-gun</city>
        <zip>910-1193</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pusan National University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University Hospital</name>
      <address>
        <city>Daegu</city>
        <zip>41944</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chonnam National University Hwasun Hospital</name>
      <address>
        <city>Jeongnam</city>
        <zip>58128</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center - PPDS</name>
      <address>
        <city>Seoul</city>
        <zip>5505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center - PPDS</name>
      <address>
        <city>Seoul</city>
        <zip>6351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea, Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>6591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematologica Alta Especialidad S.C.</name>
      <address>
        <city>Huixquilucan</city>
        <zip>52787</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Humano para Investigacion Clinica SC</name>
      <address>
        <city>Mexico</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Hematologii i Transfuzjologii</name>
      <address>
        <city>Warszawa</city>
        <state>Mazowieckie</state>
        <zip>02-776</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne, Klinika Hematologii I Transplantologii, Budynek Centrum Medycyny N</name>
      <address>
        <city>Gdansk</city>
        <state>Pomorskie</state>
        <zip>80-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne</name>
      <address>
        <city>Gdansk</city>
        <state>Pomorskie</state>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swietokrzyskie Centrum Onkologii</name>
      <address>
        <city>Kielce</city>
        <state>Swietokrzyskie</state>
        <zip>25-734</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii Ziemi Lubelskiej</name>
      <address>
        <city>Lublin</city>
        <zip>20-090</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zaklad Diagnostyki Obrazowej SOR</name>
      <address>
        <city>Opole</city>
        <zip>45-061</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Wojewodzki w Opolu</name>
      <address>
        <city>Opole</city>
        <zip>45-372</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Hospital # 40</name>
      <address>
        <city>Moscow</city>
        <zip>129301</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North-West Federal Medical Research Center n.a. V.A. Almazov</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Russian Research Institute of Hematology and Blood Transfusion</name>
      <address>
        <city>St. Petersburg</city>
        <zip>191024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO lHospitalet Hospital Duran i Reynals</name>
      <address>
        <city>LHospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>8907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Asistencial Universitario de Leon</name>
      <address>
        <city>Leon</city>
        <state>Castilla Y Leon</state>
        <zip>24071</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron - PPDS</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de La Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Maranon</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz - PPDS</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Asistencial Universitario de Salamanca - H. Clinico</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gazi University Medical Faculty Gazi Hospital</name>
      <address>
        <city>Ankara</city>
        <zip>6500</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University Medical Faculty</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mersin University Medical Faculty</name>
      <address>
        <city>Mersin</city>
        <zip>33343</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi</name>
      <address>
        <city>Samsun</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Namik Kemal University</name>
      <address>
        <city>Tekirdag</city>
        <zip>59100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karadeniz Technical University Faculty of Medicine</name>
      <address>
        <city>Trabzon</city>
        <zip>61080</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Bournemouth Hospital</name>
      <address>
        <city>Bournemouth</city>
        <state>Dorset</state>
        <zip>BH7 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maidstone Hospital</name>
      <address>
        <city>Maidstone</city>
        <state>Kent</state>
        <zip>ME16 9QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Bartholomew's Hospital</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singleton Hospital - PPDS</name>
      <address>
        <city>Swansea</city>
        <zip>SA2 8QA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>China</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f6b60294db2bf003ab499ea</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <results_first_submitted>May 25, 2022</results_first_submitted>
  <results_first_submitted_qc>August 24, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 22, 2022</results_first_posted>
  <last_update_submitted>August 22, 2023</last_update_submitted>
  <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Chronic</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Pevonedistat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 21, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT03268954/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/54/NCT03268954/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 130 investigative sites in the United States, Canada, Mexico, Australia, Belgium, Brazil, China, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Korea, Poland, Russia, Spain, Turkey, and the United Kingdom from 28 November 2017 to data cut-off date: 28 May 2021. This study is ongoing.</recruitment_details>
      <pre_assignment_details>Participants diagnosed with myelomonocytic, and myelogenous leukemia were randomized into two groups in 1:1 ratio to receive single-agent azacitidine or azacitidine + pevonedistat.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Azacitidine 75 mg/m^2</title>
          <description>Azacitidine 75 milligram per square meter (mg/m^2) intravenous (IV) or subcutaneous (SC) injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
        </group>
        <group group_id="P2">
          <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
          <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="227"/>
                <participants group_id="P2" count="227"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Population</title>
              <participants_list>
                <participants group_id="P1" count="220"/>
                <participants group_id="P2" count="223"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="227"/>
                <participants group_id="P2" count="227"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Ongoing</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="62"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="61"/>
                <participants group_id="P2" count="48"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progression to Acute Myelogenous Leukemia (AML)</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason not Specified</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT Population included all participants who were randomized.</population>
      <group_list>
        <group group_id="B1">
          <title>Azacitidine 75 mg/m^2</title>
          <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
        </group>
        <group group_id="B2">
          <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
          <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="227"/>
            <count group_id="B2" value="227"/>
            <count group_id="B3" value="454"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="73.0" spread="8.22"/>
                    <measurement group_id="B2" value="73.0" spread="7.65"/>
                    <measurement group_id="B3" value="73" spread="7.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                    <measurement group_id="B2" value="95"/>
                    <measurement group_id="B3" value="180"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="142"/>
                    <measurement group_id="B2" value="132"/>
                    <measurement group_id="B3" value="274"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="188"/>
                    <measurement group_id="B2" value="189"/>
                    <measurement group_id="B3" value="377"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                    <measurement group_id="B2" value="180"/>
                    <measurement group_id="B3" value="369"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Australia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Brazil</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>China</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Czech Republic</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Greece</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Japan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Korea, Republic of</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Turkey</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Canada</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mexico</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States of America</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="227"/>
                    <count group_id="B3" value="454"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <population>ITT Population included all participants who were randomized. Number analyzed are the number of participants with data available for height at Baseline.</population>
          <units>centimeter (cm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="225"/>
                    <count group_id="B2" value="223"/>
                    <count group_id="B3" value="448"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="167.59" spread="9.439"/>
                    <measurement group_id="B2" value="166.31" spread="10.098"/>
                    <measurement group_id="B3" value="166.95" spread="9.783"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <population>ITT Population included all participants who were randomized. Number analyzed are the number of participants with data available for weight at Baseline.</population>
          <units>kilogram (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="227"/>
                    <count group_id="B2" value="226"/>
                    <count group_id="B3" value="453"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77.65" spread="16.143"/>
                    <measurement group_id="B2" value="75.82" spread="15.996"/>
                    <measurement group_id="B3" value="76.73" spread="16.078"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Surface Area</title>
          <description>Body surface area is defined as [height (cm) × weight (kg) / 3600]^1/2</description>
          <population>ITT Population included all participants who were randomized. Number analyzed are the number of participants with data available for body surface area at Baseline.</population>
          <units>meter square (m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="225"/>
                    <count group_id="B2" value="223"/>
                    <count group_id="B3" value="448"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.89" spread="0.228"/>
                    <measurement group_id="B2" value="1.86" spread="0.233"/>
                    <measurement group_id="B3" value="1.88" spread="0.231"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Event-Free Survival (EFS)</title>
        <description>EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization [WHO] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML.</description>
        <time_frame>From randomization until transformation to acute myeloid leukemia, or death due to any cause up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-Free Survival (EFS)</title>
          <description>EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization [WHO] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML.</description>
          <population>ITT Population included all participants who were randomized.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7" lower_limit="14.42" upper_limit="19.68"/>
                    <measurement group_id="O2" value="17.7" lower_limit="13.63" upper_limit="20.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.557</p_value>
            <method>Log Rank</method>
            <method_desc>P-value comparing EFS between treatment groups was based on the 1-sided Cui-Hung-Wang weighted unstratified log-rank test.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.968</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.757</ci_lower_limit>
            <ci_upper_limit>1.238</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional hazard regression with stratification(low-blast AML,IPSS-R risk groups=very high,high,or intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:better prevention of EFS in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall survival was defined as the time from randomization to death from any cause.</description>
        <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall survival was defined as the time from randomization to death from any cause.</description>
          <population>ITT Population included all participants who were randomized.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.8" lower_limit="14.92" upper_limit="20.11"/>
                    <measurement group_id="O2" value="20.3" lower_limit="17.97" upper_limit="22.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Overall Survival (OS)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>P-value comparing OS between treatment groups was based on the 1-sided Cui-Hung-Wang weighted unstratified log-rank test.</non_inferiority_desc>
            <p_value>=0.181</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.881</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.697</ci_lower_limit>
            <ci_upper_limit>1.115</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional hazard regression with stratification(low-blast AML,IPSS-R risk groups=very high,high,or intermediate for HRMDS/CMML),treatment as factor.HR&lt;1: longer survival time in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kaplan-Meier Estimates of Six-Month Survival Rate</title>
        <description>Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented.</description>
        <time_frame>Up to Month 6</time_frame>
        <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Kaplan-Meier Estimates of Six-Month Survival Rate</title>
          <description>Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented.</description>
          <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses.</population>
          <units>percentage probability</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="174"/>
                <count group_id="O2" value="174"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.825" lower_limit="0.767" upper_limit="0.869"/>
                    <measurement group_id="O2" value="0.810" lower_limit="0.752" upper_limit="0.856"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kaplan-Meier Estimates of One-Year Survival Rate</title>
        <description>Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented.</description>
        <time_frame>Up to Year 1</time_frame>
        <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Kaplan-Meier Estimates of One-Year Survival Rate</title>
          <description>Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented.</description>
          <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses.</population>
          <units>percentage probability</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="141"/>
                <count group_id="O2" value="137"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.693" lower_limit="0.626" upper_limit="0.751"/>
                    <measurement group_id="O2" value="0.646" lower_limit="0.578" upper_limit="0.706"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30</title>
        <description>30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug.</description>
        <time_frame>Up to Day 30</time_frame>
        <population>Safety Population included all enrolled participants who received at least 1 dose of azacitidine alone or pevonedistat + azacitidine.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30</title>
          <description>30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug.</description>
          <population>Safety Population included all enrolled participants who received at least 1 dose of azacitidine alone or pevonedistat + azacitidine.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="220"/>
                <count group_id="O2" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60</title>
        <description>60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug.</description>
        <time_frame>Up to Day 60</time_frame>
        <population>Safety Population included all enrolled participants who received at least 1 dose of azacitidine alone or pevonedistat + azacitidine.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60</title>
          <description>60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug.</description>
          <population>Safety Population included all enrolled participants who received at least 1 dose of azacitidine alone or pevonedistat + azacitidine.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="220"/>
                <count group_id="O2" value="223"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants</title>
        <description>Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.</description>
        <time_frame>From randomization until transformation to AML till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the given category.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants</title>
          <description>Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.</description>
          <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the given category.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="174"/>
                <count group_id="O2" value="177"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HR MDS Participants</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="163"/>
                    <count group_id="O2" value="161"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.6" lower_limit="26.51" upper_limit="NA">The upper limit of 95% confidence interval (CI) was not estimable due to low number of participants with event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="23.29" upper_limit="NA">The median, and upper limit of 95% CI were not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HR CMML Participants</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">The median, lower limit, and upper limit of 95% CI were not estimable due to low number of participants with event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">The median, lower limit, and upper limit of 95% CI were not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HR MDS/CMML Participants</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="177"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.6" lower_limit="29.04" upper_limit="NA">The upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="24.28" upper_limit="NA">The median, and upper limit of 95% CI were not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Time to AML Transformation in HR MDS Participants</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.562</p_value>
            <p_value_desc>P-value comparing time to AML Transformation between treatment groups was based on 1-sided stratified log-rank test stratified by IPSS-R risk groups of very high, high, or intermediate for HR MDS.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.037</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.660</ci_lower_limit>
            <ci_upper_limit>1.630</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional HazardRegression with stratification(IPSS-R risk groups=very high,high,or intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:better prevention of AML transformation in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Time to AML Transformation in HR CMML Participants</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.603</p_value>
            <p_value_desc>P-value comparing time to AML Transformation between treatment groups was based on 1-sided stratified log-rank test stratified by IPSS-R risk groups of very high, high, or intermediate for HR CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.512</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.068</ci_lower_limit>
            <ci_upper_limit>33.773</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional HazardRegression with stratification(IPSS-R risk groups=very high,high,or intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:better prevention of AML transformation in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Time to AML Transformation in HR MDS/CMML Participants</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.558</p_value>
            <p_value_desc>P-value comparing time to AML Transformation between treatment groups was based on 1-sided stratified log-rank test stratified by IPSS-R risk groups of very high, high, or intermediate for HR CMML/MDS.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.034</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.663</ci_lower_limit>
            <ci_upper_limit>1.610</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional HazardRegression with stratification(IPSS-R risk groups=very high,high,or intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:better prevention of AML transformation in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)</title>
        <description>CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 gram per deciliter (g/dL) hemoglobin (Hgb),&gt;=100*10^9/liter (/L) platelets (pl),&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
        <time_frame>From randomization until CR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>Response-Evaluable Population (REP) included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)</title>
          <description>CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 gram per deciliter (g/dL) hemoglobin (Hgb),&gt;=100*10^9/liter (/L) platelets (pl),&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
          <population>Response-Evaluable Population (REP) included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71"/>
                    <measurement group_id="O2" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Number of Participants With Complete Remission (CR) and CR+Complete Remission with Incomplete Blood Count Recovery (CRi)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.374</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-4.18</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.18</ci_lower_limit>
            <ci_upper_limit>4.83</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With CR and Marrow CR</title>
        <description>Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and &gt;=11 g/dL Hgb, &gt;=100*10^9/L platelets (pl), &gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment.</description>
        <time_frame>From randomization until CR or marrow CR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With CR and Marrow CR</title>
          <description>Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and &gt;=11 g/dL Hgb, &gt;=100*10^9/L platelets (pl), &gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)</title>
        <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%. HI: Hgb increase &gt;=1.5 g/dL if &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline&gt;20*10^9/L or increase from &lt;20*10^9/L to &gt;20*10^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
        <time_frame>From randomization until, CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)</title>
          <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%. HI: Hgb increase &gt;=1.5 g/dL if &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline&gt;20*10^9/L or increase from &lt;20*10^9/L to &gt;20*10^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77"/>
                    <measurement group_id="O2" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With CR and Marrow CR and PR</title>
        <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%.</description>
        <time_frame>From randomization until CR or Marrow CR and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With CR and Marrow CR and PR</title>
          <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)</title>
        <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still&gt;5%. HI: Hgb increase &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline&gt;20*10^9/L or increases from &lt;20*10^9/L to &gt;20*10^9/L and by at least 100%; neutrophil increases by 100% and absolute increases of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
        <time_frame>From randomization until CR, marrow CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)</title>
          <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: &lt;=5% myeloblasts and decrease by &gt;=50% over pretreatment. PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still&gt;5%. HI: Hgb increase &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline&gt;20*10^9/L or increases from &lt;20*10^9/L to &gt;20*10^9/L and by at least 100%; neutrophil increases by 100% and absolute increases of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112"/>
                    <measurement group_id="O2" value="117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Overall Response (OR)</title>
        <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR or PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still&gt;5%. For low-blast AML-CR:morphologic leukemia-free state&gt;1.0*10^9 neutrophils, &gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but &gt;=50% decrease in bone marrow aspirate.</description>
        <time_frame>From randomization until CR and PR or CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Overall Response (OR)</title>
          <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR or PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still&gt;5%. For low-blast AML-CR:morphologic leukemia-free state&gt;1.0*10^9 neutrophils, &gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but &gt;=50% decrease in bone marrow aspirate.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Number of Participants with OR</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.329</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test stratified by low-blast AML, Revised International Prognostic Scoring System (IPSS-R) risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-4.67</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.72</ci_lower_limit>
            <ci_upper_limit>4.39</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Overall Response 2 (OR2)</title>
        <description>OR2=participant with best overall response of CR+PR+HI in HR MDS/CMML participants,or of CR+CRi+PR in low-blast AML participants.CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still &gt;5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)&lt;11 g/dL;pl inc≥30*10^9/L if BL&gt;20*10^9/L or inc from &lt;20*10^9/L to &gt;20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of &gt;0.5*10^9/L if BL&lt;100*10^9/L.For low-blast AML-CR:morphologic leukemia-free state &gt;1.0*10^9 neutrophils,≥100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl&lt;100*10^9/L;PR:all CR hematological values but ≥50% decrease in BM aspirate.Number of responders determined by independent review committee(IRC) assessment.</description>
        <time_frame>From randomization until, CR, PR or HI or CR, CRi or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP: all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for responders. Three participants were not counted as responders for OR2 as the IRC assessed these participants as non-responders.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Overall Response 2 (OR2)</title>
          <description>OR2=participant with best overall response of CR+PR+HI in HR MDS/CMML participants,or of CR+CRi+PR in low-blast AML participants.CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still &gt;5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)&lt;11 g/dL;pl inc≥30*10^9/L if BL&gt;20*10^9/L or inc from &lt;20*10^9/L to &gt;20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of &gt;0.5*10^9/L if BL&lt;100*10^9/L.For low-blast AML-CR:morphologic leukemia-free state &gt;1.0*10^9 neutrophils,≥100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl&lt;100*10^9/L;PR:all CR hematological values but ≥50% decrease in BM aspirate.Number of responders determined by independent review committee(IRC) assessment.</description>
          <population>REP: all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for responders. Three participants were not counted as responders for OR2 as the IRC assessed these participants as non-responders.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94"/>
                    <measurement group_id="O2" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Number of Participants with OR2</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.891</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-0.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.03</ci_lower_limit>
            <ci_upper_limit>9.15</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Complete Remission (CR)</title>
        <description>Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
        <time_frame>From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for participants with complete remission.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Complete Remission (CR)</title>
          <description>Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for participants with complete remission.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" lower_limit="6.93" upper_limit="29.08"/>
                    <measurement group_id="O2" value="17.2" lower_limit="13.96" upper_limit="NA">The upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of CR</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.072</p_value>
            <method>Log Rank</method>
            <method_desc>P-value was based on 1-sided log-rank test stratified by low-blast AML,IPSS-R risk groups of very high,high,or intermediate for HR MDS/CMML.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.679</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.402</ci_lower_limit>
            <ci_upper_limit>1.146</ci_upper_limit>
            <estimate_desc>Hazard ratio was based on an unadjusted stratified Cox proportional hazard regression model with stratification factors (low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML) and treatment as a factor in the model.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)</title>
        <description>Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). Disease responses for low-blast AML were based on the Revised IWG Response Criteria for AML. CR is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 g/dL hemoglobin (Hgb),&gt;=100*10^9/liter (/L) platelets (pl),&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
        <time_frame>From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for participants with CR and CRi.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)</title>
          <description>Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). Disease responses for low-blast AML were based on the Revised IWG Response Criteria for AML. CR is defined as &lt;=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to &gt;=11 g/dL hemoglobin (Hgb),&gt;=100*10^9/liter (/L) platelets (pl),&gt;=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of &gt;=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (&lt;1.0*10^9/L) or thrombocytopenia (pl&lt;100*10^9/L).</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for participants with CR and CRi.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" lower_limit="3.02" upper_limit="NA">The upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                    <measurement group_id="O2" value="15.0" lower_limit="3.94" upper_limit="NA">The upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of Complete Remission + Complete Remission with Incomplete Blood Count Recovery (CRi)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.373</p_value>
            <p_value_desc>P-value comparing duration of CR+CRi between treatment groups was based on 1-sided unstratified log-rank.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.846</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.306</ci_lower_limit>
            <ci_upper_limit>2.339</ci_upper_limit>
            <estimate_desc>Hazard ratio was based on an unadjusted unstratified Cox proportional hazard regression model with treatment as a factor in the model.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Overall Response (OR)</title>
        <description>Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR+PR for HR MDS/CMML and CR+Cri+ PR for low-blast AML.CR for HR MDS/CMML:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR:all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still &gt;5%. For low-blast AML-CR: morphologic leukemia-free state &gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with CRi: fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but &gt;=50% decrease in % of blasts in bone marrow aspirate.</description>
        <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for responders.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Overall Response (OR)</title>
          <description>Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR+PR for HR MDS/CMML and CR+Cri+ PR for low-blast AML.CR for HR MDS/CMML:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR:all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still &gt;5%. For low-blast AML-CR: morphologic leukemia-free state &gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with CRi: fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but &gt;=50% decrease in % of blasts in bone marrow aspirate.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Data is reported for responders.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.3" lower_limit="8.31" upper_limit="NA">The upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                    <measurement group_id="O2" value="17.1" lower_limit="12.68" upper_limit="NA">The upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of Overall Response (OR)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.320</p_value>
            <p_value_desc>P-value comparing duration of PR or better response between treatment groups was based on 1-sided log-rank test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.889</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.542</ci_lower_limit>
            <ci_upper_limit>1.458</ci_upper_limit>
            <estimate_desc>Hazard ratio was based on an unadjusted stratified Cox proportional hazard regression model with stratification factors (low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML) and treatment as a factor in the model.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Overall Response 2 (OR2)</title>
        <description>Duration of OR2: from date of first documentation of CR+PR+HI to first documentation of PD/relapse after CR/PR for responders of CR+PR+HI for HR MDS/CMML and CR,CRi,PR for low-blast AML. For HR MDS/CMML-CR:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb, &gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment, still &gt;5%; HI:Hgb inc &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl inc&gt;=30*10^9/L if baseline&gt;20*10^9/L or inc from&lt;20*10^9/L to&gt;20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.For low-blast AML-CR: morphologic leukemia-free state,&gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi: fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl &lt;100*10^9/L;PR:all CR hematological values but&gt;=50% decrease in bone marrow aspirate.</description>
        <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Three participants who were non-responders (for OR2) as per the IRC were included in this outcome measure as they had assessment of HI and duration of OR2 for these participants could still be derived based on the pre-specified criteria for HR MDS/CMML participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Overall Response 2 (OR2)</title>
          <description>Duration of OR2: from date of first documentation of CR+PR+HI to first documentation of PD/relapse after CR/PR for responders of CR+PR+HI for HR MDS/CMML and CR,CRi,PR for low-blast AML. For HR MDS/CMML-CR:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb, &gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment, still &gt;5%; HI:Hgb inc &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl inc&gt;=30*10^9/L if baseline&gt;20*10^9/L or inc from&lt;20*10^9/L to&gt;20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.For low-blast AML-CR: morphologic leukemia-free state,&gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi: fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl &lt;100*10^9/L;PR:all CR hematological values but&gt;=50% decrease in bone marrow aspirate.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Three participants who were non-responders (for OR2) as per the IRC were included in this outcome measure as they had assessment of HI and duration of OR2 for these participants could still be derived based on the pre-specified criteria for HR MDS/CMML participants.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.3" lower_limit="11.17" upper_limit="30.92"/>
                    <measurement group_id="O2" value="18.9" lower_limit="15.01" upper_limit="NA">The upper limit of 95% CI was not estimable due to lower number of participants with the event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of Overall Response 2 (OR2)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.151</p_value>
            <p_value_desc>P-value comparing duration of overall response 2 between treatment groups was based on 1-sided log-rank test stratified by low blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.796</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.514</ci_lower_limit>
            <ci_upper_limit>1.231</ci_upper_limit>
            <estimate_desc>Hazard ratio was based on an unadjusted stratified Cox proportional hazard regression model with stratification factors (low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML) and treatment as a factor in the model.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence</title>
        <description>A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline.</description>
        <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants from a subset of the ITT Population who were transfusion dependent at Baseline. Number analyzed is the number of participants who were transfusion dependent at Baseline for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence</title>
          <description>A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline.</description>
          <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants from a subset of the ITT Population who were transfusion dependent at Baseline. Number analyzed is the number of participants who were transfusion dependent at Baseline for the specified category.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
                <count group_id="O2" value="129"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Percentage of Participants With RBCs-transfusion Independence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="131"/>
                    <count group_id="O2" value="122"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.3"/>
                    <measurement group_id="O2" value="47.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percentage of Participants With Platelet-transfusion Independence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.9"/>
                    <measurement group_id="O2" value="45.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Percentage of Participants With RBC-transfusion Independence</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.573</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>3.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.02</ci_lower_limit>
            <ci_upper_limit>15.55</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Percentage of Participants With Platelet-transfusion Independence</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.477</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-3.43</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-25.84</ci_lower_limit>
            <ci_upper_limit>18.97</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence</title>
        <description>Duration of RBC and platelet transfusion independence was defined as the longest time between the last RBC and/or platelet transfusion before the start of the RBC and/or platelet transfusion-independent period and the first RBC and/or platelet transfusion after the start of the transfusion-independent period, which occurs &gt;= 8 weeks later.</description>
        <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized. Number analyzed is the number of participants who achieved transfusion independence for the specified category, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence</title>
          <description>Duration of RBC and platelet transfusion independence was defined as the longest time between the last RBC and/or platelet transfusion before the start of the RBC and/or platelet transfusion-independent period and the first RBC and/or platelet transfusion after the start of the transfusion-independent period, which occurs &gt;= 8 weeks later.</description>
          <population>ITT Population included all participants who were randomized. Number analyzed is the number of participants who achieved transfusion independence for the specified category, with data available for analysis.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Duration of RBC Transfusion Independence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                    <count group_id="O2" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.6" lower_limit="10.18" upper_limit="28.09"/>
                    <measurement group_id="O2" value="13.5" lower_limit="9.07" upper_limit="16.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Duration of Platelet Transfusion Independence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.9" lower_limit="5.09" upper_limit="23.23"/>
                    <measurement group_id="O2" value="11.6" lower_limit="2.73" upper_limit="16.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Duration of Transfusion Independence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="63"/>
                    <count group_id="O2" value="59"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0" lower_limit="8.90" upper_limit="19.48"/>
                    <measurement group_id="O2" value="13.5" lower_limit="10.38" upper_limit="16.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of RBC Transfusion Independence</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.774</p_value>
            <p_value_desc>P-value comparing duration of RBC or platelet transfusion between treatment groups was based on 1-sided log-rank test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.231</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.715</ci_lower_limit>
            <ci_upper_limit>2.119</ci_upper_limit>
            <estimate_desc>HR:unadjusted Cox Proportional Hazard regression;stratification(low-blast AML,IPSS-R risk groups=very high,high,intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:longer duration of transfusion independence in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of Platelet Transfusion Independence</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.801</p_value>
            <p_value_desc>P-value comparing duration of platelet transfusion between treatment groups was based on 1-sided log-rank test stratified by low blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.533</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.567</ci_lower_limit>
            <ci_upper_limit>4.147</ci_upper_limit>
            <estimate_desc>HR:unadjusted Cox Proportional Hazard regression;stratification(low-blast AML,IPSS-R risk groups=very high,high,intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:longer duration of transfusion independence in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Duration of Transfusion Independence</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.450</p_value>
            <p_value_desc>P-value comparing duration of RBC or platelet transfusion between treatment groups was based on 1-sided log-rank test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.968</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.580</ci_lower_limit>
            <ci_upper_limit>1.614</ci_upper_limit>
            <estimate_desc>HR:unadjusted Cox Proportional Hazard regression;stratification(low-blast AML,IPSS-R risk groups=very high,high,intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:longer duration of transfusion independence in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)</title>
        <description>Time to first CR or PR is defined as the time from randomization to first documented CR or PR, whichever occurs first. Disease responses for HR MDS or CMML or low-blast AML cycle 6 are based on Modified IWG Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. For HR MDS or CMML-CR:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still&gt;5%; For low-blast AML-CR: morphologic leukemia-free state,&gt;1.0*10^9/L neutrophils, pl&gt;=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.</description>
        <time_frame>From randomization until CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)</title>
          <description>Time to first CR or PR is defined as the time from randomization to first documented CR or PR, whichever occurs first. Disease responses for HR MDS or CMML or low-blast AML cycle 6 are based on Modified IWG Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. For HR MDS or CMML-CR:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11 g/dL Hgb,&gt;=100*10^9/L pl,&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still&gt;5%; For low-blast AML-CR: morphologic leukemia-free state,&gt;1.0*10^9/L neutrophils, pl&gt;=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl &lt;100*10^9/L; PR: all CR hematological values but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="12.12" upper_limit="NA">The median, and upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="24.61" upper_limit="NA">The median, and upper limit of 95% CI was not estimable due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission with Incomplete Blood Count Recovery (CRi)</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.228</p_value>
            <p_value_desc>P-value comparing time to first CR or PR or CRi (low-blast AML) between treatment groups was based on 1-sided stratified log-rank test stratified by low-blast AML,IPSS-R risk groups of very high,high,or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.880</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.628</ci_lower_limit>
            <ci_upper_limit>1.234</ci_upper_limit>
            <estimate_desc>Hazard ratio was based on an unadjusted stratified Cox proportional hazard regression model with stratification factors (low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML) and treatment as a factor in the model.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Hematologic Improvement (HI)</title>
        <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline &gt;20*10^9/L or increase from &lt;20*10^9/L to &gt;20*10^9/L by at least 100%; neutrophil increase by 100% and absolute increase of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
        <time_frame>From randomization until HI till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a baseline and at least 1 postbaseline disease assessment. Overall number analyzed are the number of participants with data available for analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Hematologic Improvement (HI)</title>
          <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase &gt;=1.5 g/dL if baseline &lt;11 g/dL; pl increase &gt;=30*10^9/L if baseline &gt;20*10^9/L or increase from &lt;20*10^9/L to &gt;20*10^9/L by at least 100%; neutrophil increase by 100% and absolute increase of &gt;0.5*10^9/L if baseline &lt;1.0*10^9/L.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a baseline and at least 1 postbaseline disease assessment. Overall number analyzed are the number of participants with data available for analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="157"/>
                <count group_id="O2" value="163"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Number of Participants With HI</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.320</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-5.46</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.36</ci_lower_limit>
            <ci_upper_limit>5.44</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML</title>
        <description>Inpatient hospital admission data was collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurred first. Transformation to AML is defined, according to WHO Classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.</description>
        <time_frame>From randomization until transformation to AML or until initiation of subsequent therapy till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML</title>
          <description>Inpatient hospital admission data was collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurred first. Transformation to AML is defined, according to WHO Classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.</description>
          <population>ITT Population included all participants who were randomized.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Rate Difference</param_type>
            <param_value>2.64</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.30</ci_lower_limit>
            <ci_upper_limit>5.58</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progressive Disease (PD), Relapse After CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death</title>
        <description>Time to PD, relapse after CR(low-blast AML), relapse after CR or PR(HR MDS/CMML), or death,defined as time from date of randomization until date of first documentation of PD,relapse after CR(low-blast AML),relapse after CR or PR(HR MDS/CMML),or death due to any cause, whichever occurs first. In HR MDS/CMML,PD: Participants with&lt;5% blasts:&gt;=50% inc &gt;5% blasts, with 5%-9% blasts:&gt;=50% inc&gt;10% blasts, with 10%-19% blasts:&gt;=50% inc &gt;20% blasts,with 20%-30% blasts, at least 50% decrement from maximum remission/response in granulocytes or pl or reduction in Hgb by&gt;=2 g/dL/new transfusion dependence.Relapse after CR or PR: return to pretreatment bone marrow blast %/Decrement of &gt;=50% from maximum remission/response levels in granulocytes/pl/reduction in Hgb conc.&gt;=1.5 g/dL/transfusion dependence. In AML,PD:&gt;50% inc in bone marrow blasts to &gt;30% blasts,&gt;50% inc in circulating blasts to&gt;30% blasts in peripheral blood, Development of extramedullary disease/new sites of extramedullary leukemia.</description>
        <time_frame>From randomization until PD, relapse after CR, or relapse after CR or PR, or death due to any cause, whichever occurs first till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progressive Disease (PD), Relapse After CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death</title>
          <description>Time to PD, relapse after CR(low-blast AML), relapse after CR or PR(HR MDS/CMML), or death,defined as time from date of randomization until date of first documentation of PD,relapse after CR(low-blast AML),relapse after CR or PR(HR MDS/CMML),or death due to any cause, whichever occurs first. In HR MDS/CMML,PD: Participants with&lt;5% blasts:&gt;=50% inc &gt;5% blasts, with 5%-9% blasts:&gt;=50% inc&gt;10% blasts, with 10%-19% blasts:&gt;=50% inc &gt;20% blasts,with 20%-30% blasts, at least 50% decrement from maximum remission/response in granulocytes or pl or reduction in Hgb by&gt;=2 g/dL/new transfusion dependence.Relapse after CR or PR: return to pretreatment bone marrow blast %/Decrement of &gt;=50% from maximum remission/response levels in granulocytes/pl/reduction in Hgb conc.&gt;=1.5 g/dL/transfusion dependence. In AML,PD:&gt;50% inc in bone marrow blasts to &gt;30% blasts,&gt;50% inc in circulating blasts to&gt;30% blasts in peripheral blood, Development of extramedullary disease/new sites of extramedullary leukemia.</description>
          <population>ITT Population included all participants who were randomized.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8" lower_limit="10.25" upper_limit="13.31"/>
                    <measurement group_id="O2" value="13.1" lower_limit="11.01" upper_limit="15.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Time to Progressive Disease (PD), Relapse after CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.084</p_value>
            <p_value_desc>P-value was obtained from a stratified 1-sided log-rank test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.858</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.689</ci_lower_limit>
            <ci_upper_limit>1.067</ci_upper_limit>
            <estimate_desc>Hazard ratio was based on a stratified Cox proportional hazard regression model stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML, with treatment as a factor in the model.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30</title>
        <description>The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The percentage of participants for each parameter score were categorized as improved, stable, and worsened. Only categories with at least one participant with event are reported.</description>
        <time_frame>Up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized. All participants with patient-reported outcome (PRO) measurements at Baseline, at least one post-baseline visit, and with data available for analyses were analyzed for this outcome measure and are included as the overall number of participants analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30</title>
          <description>The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The percentage of participants for each parameter score were categorized as improved, stable, and worsened. Only categories with at least one participant with event are reported.</description>
          <population>ITT Population included all participants who were randomized. All participants with patient-reported outcome (PRO) measurements at Baseline, at least one post-baseline visit, and with data available for analyses were analyzed for this outcome measure and are included as the overall number of participants analyzed.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Global Health Status/QOL Score: Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global Health Status/QOL Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Functioning Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Functioning Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Functioning Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Role Functioning Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Functioning Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Functioning Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive Functioning Score: Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive Functioning Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Functioning Score: Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social Functioning Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea/Vomiting Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea/Vomiting Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnoea Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnoea Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Loss Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation Score: Improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhoea Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhoea Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Financial Difficulties Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QLQ-C30 Summary Score: Stable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="2.5" upper_limit="100"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QLQ-C30 Summary Score: Worsened</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="2.5" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.002</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.750</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.615</ci_lower_limit>
            <ci_upper_limit>0.913</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Concentration of Pevonedistat</title>
        <time_frame>Cycle 1 Day 1 predose and multiple time points (up to 4 hours) post dose; Cycle 1 Days 3 and 5 predose; Cycle 2 and 4 Day 1 at multiple time points (up to 3 hours) post dose; Cycle 4 Day 3 predose (Cycle length= 28 days)</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Overall Response in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</title>
        <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR + PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still&gt;5%. For low-blast AML-CR: morphologic leukemia-free state, &gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl&lt;100*10^9/L; PR: all CR hematological values but&gt;=50% decrease in the percentage of blasts to 5% to 25% in bone marrow aspirate.</description>
        <time_frame>From randomization until CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses. Number analyzed are the number of participants with data available for analysis for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Overall Response in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</title>
          <description>Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR + PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: &lt;=5% myeloblasts with normal maturation of all bone marrow cell lines, &gt;=11 g/dL Hgb, &gt;=100*10^9/L pl, &gt;=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts&gt;=50% decrease over pretreatment but still&gt;5%. For low-blast AML-CR: morphologic leukemia-free state, &gt;1.0*10^9 neutrophils,&gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia&lt;1.0*10^9/L or pl&lt;100*10^9/L; PR: all CR hematological values but&gt;=50% decrease in the percentage of blasts to 5% to 25% in bone marrow aspirate.</description>
          <population>ITT Population included all participants who were randomized. Overall number analyzed are the number of participants with data available for analyses. Number analyzed are the number of participants with data available for analysis for the specified category.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>OR: HR MDS/CMML Participants</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                    <count group_id="O2" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OR: Low-blast AML Participants</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>OR: HR MDS/CMML Participants</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.683</p_value>
            <p_value_desc>P-value for HR MDS/CMML was obtained from a stratified Cochran-Mantel-Haenszel chi-square test</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-2.85</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-19.44</ci_lower_limit>
            <ci_upper_limit>13.75</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>ORR: Low-blast AML Participants</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.840</p_value>
            <p_value_desc>P-value for Low-blast AML was obtained from an unstratified Cochran-Mantel-Haenszel chi-square test.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>2.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20.39</ci_lower_limit>
            <ci_upper_limit>25.12</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Event-Free Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</title>
        <description>Event was defined as death or transformation to AML in participants with MDS or CMML, whichever occurred first. Transformation to AML was defined, according to World Health Organization (WHO) Classification as a participant having &gt;20% blasts in the blood or marrow and increase of blast count by 50%. Event was defined as death in participants with low-blast AML.</description>
        <time_frame>From randomization until transformation to AML if eligible or death till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-Free Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</title>
          <description>Event was defined as death or transformation to AML in participants with MDS or CMML, whichever occurred first. Transformation to AML was defined, according to World Health Organization (WHO) Classification as a participant having &gt;20% blasts in the blood or marrow and increase of blast count by 50%. Event was defined as death in participants with low-blast AML.</description>
          <population>ITT Population included all participants who were randomized.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8" lower_limit="8.44" upper_limit="14.32"/>
                    <measurement group_id="O2" value="14.6" lower_limit="9.99" upper_limit="18.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Event-Free Survival in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.240</p_value>
            <p_value_desc>P-value comparing EFS between treatment groups was based on 1-sided log-rank test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.877</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.608</ci_lower_limit>
            <ci_upper_limit>1.263</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional hazard regression with stratification factors (IPSS-R risk groups=very high,high,or intermediate for HRMDS/CMML),treatment as factor.HR&lt;1:better prevention of EFS in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</title>
        <description>OS was calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored as of the date the participant was last known to be alive.</description>
        <time_frame>From randomization until death till data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
        <population>ITT Population included all participants who were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group</title>
          <description>OS was calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored as of the date the participant was last known to be alive.</description>
          <population>ITT Population included all participants who were randomized.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="227"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8" lower_limit="10.84" upper_limit="14.78"/>
                    <measurement group_id="O2" value="16.1" lower_limit="11.40" upper_limit="20.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Overall Survival in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.145</p_value>
            <p_value_desc>P-value comparing OS between treatment groups was based on 1-sided log-rank test stratified by low-blast AML, IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.826</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.580</ci_lower_limit>
            <ci_upper_limit>1.178</ci_upper_limit>
            <estimate_desc>HR:unadjusted stratified Cox proportional hazard regression with stratification factors(IPSS-R risk groups of very high,high,intermediate) and treatment as factor in model.HR&lt;1: longer survival time in combination arm than azacitidine arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Overall Response by Cycle 6</title>
        <description>Responses for HR MDS/CMML are based on Modified International Working Group (IWG) Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR and PR for HR MDS/CMML and CR+CR with incomplete blood count recovery(CRi)+PR for low-blast AML. CR for HR MDS/CMML:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11g/dL hemoglobin (Hgb),&gt;=100*10^9/L platelet (pl),&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood, and PR:all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%. For low-blast AML-CR:morphologic leukemia-free state,&gt;1.0*10^9 neutrophils, &gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L/thrombocytopenia (pl&lt;100*10^9/L); PR:all CR hematological values but&gt;=50% decrease in percentage of blasts to 5%-25% in bone marrow aspirate.</description>
        <time_frame>Up to Cycle 6 (up to approximately Day 168)</time_frame>
        <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Number analyzed is the number of participants with data available for analysis for the specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
          <group group_id="O2">
            <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
            <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Overall Response by Cycle 6</title>
          <description>Responses for HR MDS/CMML are based on Modified International Working Group (IWG) Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR and PR for HR MDS/CMML and CR+CR with incomplete blood count recovery(CRi)+PR for low-blast AML. CR for HR MDS/CMML:&lt;=5% myeloblasts with normal maturation of all bone marrow cell lines,&gt;=11g/dL hemoglobin (Hgb),&gt;=100*10^9/L platelet (pl),&gt;=1.0*10^9/L neutrophils, 0% blasts in peripheral blood, and PR:all CR criteria met except bone marrow blasts &gt;=50% decrease over pretreatment but still &gt;5%. For low-blast AML-CR:morphologic leukemia-free state,&gt;1.0*10^9 neutrophils, &gt;=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia &lt;1.0*10^9/L/thrombocytopenia (pl&lt;100*10^9/L); PR:all CR hematological values but&gt;=50% decrease in percentage of blasts to 5%-25% in bone marrow aspirate.</description>
          <population>REP included all participants who received at least 1 dose of study drug and had a Baseline and at least 1 postbaseline disease assessment. Number analyzed is the number of participants with data available for analysis for the specified category.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall Response for HR MDS/CMML</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="157"/>
                    <count group_id="O2" value="163"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall Response for Low-blast AML</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Overall Response for HR MDS/CMML</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.261</p_value>
            <p_value_desc>P-value was obtained from a stratified Cochran-Mantel-Haenszel chi-square test stratified by IPSS-R risk groups of very high, high, or intermediate for HR MDS/CMML.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>-5.14</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.95</ci_lower_limit>
            <ci_upper_limit>3.68</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Overall Response for Low-blast AML</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.026</p_value>
            <p_value_desc>P-value was obtained from an unstratified Cochran-Mantel-Haenszel chi-square test.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Absolute Rate Difference</param_type>
            <param_value>22.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.22</ci_lower_limit>
            <ci_upper_limit>41.49</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug up to data cut-off date: 28 May 2021 (up to approximately 42 months)</time_frame>
      <desc>At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. All-cause mortality=ITT Population (all participants who were randomized). Serious Adverse Events and Other Adverse Events=Safety Population [all participants who received at least 1 dose of study drug (i.e., pevonedistat + azacitidine or single-agent azacitidine)].</desc>
      <group_list>
        <group group_id="E1">
          <title>Azacitidine 75 mg/m^2</title>
          <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
        </group>
        <group group_id="E2">
          <title>Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2</title>
          <description>Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="144" subjects_at_risk="227"/>
                <counts group_id="E2" subjects_affected="141" subjects_at_risk="227"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="142" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="153" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Blood loss anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Thrombocytopenic purpura</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Leukostasis syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pure white cell aplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Disseminated intravascular coagulation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Lymphadenitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Splenic infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cardiopulmonary failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Silent myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cardiovascular insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Deafness unilateral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Neutropenic colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Intestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Gastric disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Gastrointestinal angiodysplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Gastrointestinal vascular malformation haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Incarcerated inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Small intestinal ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Visceral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Medical device site inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="32" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Abdominal sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pulmonary sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis septic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Abscess limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Perichondritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Colonic abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Rectal abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Escherichia bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Escherichia infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Escherichia sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection fungal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pulmonary mycosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary aspergillosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hepatic cyst infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Liver abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Klebsiella bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Epididymitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cellulitis staphylococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Staphylococcal sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumonia viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Arthritis infective</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Vulvitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumonia legionella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Listeriosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumonia pseudomonal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pseudomonal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Serratia bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Subdural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Soft tissue injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Traumatic haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Central nervous system injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cervical vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Refractoriness to platelet transfusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hyphaema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Occult blood</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Tumour lysis syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hyperferritinaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Soft tissue necrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Chest wall haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Spondylitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acute myeloid leukaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Myelodysplastic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Tumour associated fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Central nervous system haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cerebral haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haemorrhagic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Intracranial haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Altered state of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Guillain-Barre syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Dementia with Lewy bodies</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hepatic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Paraparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Product contamination microbial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Urinary bladder polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Urethral stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Ureterolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Acute pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pulmonary congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haemothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hydrothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Organising pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Lung infiltration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Bronchiectasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pharyngeal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acute febrile neutrophilic dermatosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Shock haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="216" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="215" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="82" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="77" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="77" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="70" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="71" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="90" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="82" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="78" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="51" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="60" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="51" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="55" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="53" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Abnormal loss of weight</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="223"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="220"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="223"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Takeda</organization>
      <phone>+1-877-825-3327</phone>
      <email>TrialDisclosures@takeda.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03268954
org study id: Pevonedistat-3001
secondary id: 2017-000318-40
secondary id: U1111-1189-8055
secondary id: MOH_2018-02-04_002154
secondary id: JapicCTI-183848
secondary id: NCI-2017-02059
nct id: NCT03268954
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine whether the combination of pevonedistat and
      azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine.
      (An event is defined as death or transformation to AML in participants with MDS or CMML,
      whichever occurs first, and is defined as death in participants with low-blast AML).
The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to
      treat people with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic
      leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment
      with azacitidine. This study will look at the overall survival, event-free survival and
      response to treatment in people who take pevonedistat and azacitidine when compared to people
      who take single-agent azacitidine.

      The study will enroll approximately 450 participants. Once enrolled, participants will be
      randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment
      groups in 28-day treatment cycles:

        -  Pevonedistat 20 mg/m^2 and azacitidine 75 mg/m^2 combination

        -  Single-agent azacitidine 75 mg/m^2

      All participants will receive azacitidine via intravenous or subcutaneous route. Participants
      randomized to the combination arm will also receive pevonedistat intravenous infusion.

      This multi-center trial will be conducted Spain, Belgium, Brazil, Canada, Czech Republic,
      France, Germany, Israel, Italy, the United States, Australia, Greece, Japan, Mexico, Poland,
      Russia, Korea, Turkey, China and United Kingdom. The overall time to participate in this
      study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days
      after the last dose of study drug or before the start of subsequent anti-neoplastic therapy
      if that occurs sooner.

      Participants with HR MDS or CMML will have EFS follow-up study visits every month if their
      disease has not transformed to AML and they have not started subsequent therapy. Participants
      with low-blast AML will have response follow-up study visits every month until they relapse
      from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted
      every 3 months) when they have confirmed transformation to AML (for participants with HR MDS
      or CMML at enrollment) or experienced PD (for participants with low-blast AML at study
      enrollment).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Event-Free Survival (EFS)
time frame: From randomization until transformation to acute myeloid leukemia, or death due to any cause up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization [WHO] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML.
measure: Overall Survival (OS)
time frame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Overall survival was defined as the time from randomization to death from any cause.
measure: Kaplan-Meier Estimates of Six-Month Survival Rate
time frame: Up to Month 6
description: Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented.
measure: Kaplan-Meier Estimates of One-Year Survival Rate
time frame: Up to Year 1
description: Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented.
measure: Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30
time frame: Up to Day 30
description: 30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug.
measure: Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60
time frame: Up to Day 60
description: 60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug.
measure: Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants
time frame: From randomization until transformation to AML till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.
measure: Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)
time frame: From randomization until CR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 gram per deciliter (g/dL) hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).
measure: Number of Participants With CR and Marrow CR
time frame: From randomization until CR or marrow CR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and >=11 g/dL Hgb, >=100*10^9/L platelets (pl), >=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment.
measure: Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)
time frame: From randomization until, CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%. HI: Hgb increase >=1.5 g/dL if <11 g/dL; pl increase >=30*10^9/L if baseline>20*10^9/L or increase from <20*10^9/L to >20*10^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of >0.5*10^9/L if baseline <1.0*10^9/L.
measure: Number of Participants With CR and Marrow CR and PR
time frame: From randomization until CR or Marrow CR and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%.
measure: Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)
time frame: From randomization until CR, marrow CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still>5%. HI: Hgb increase >=1.5 g/dL if baseline <11 g/dL; pl increase >=30*10^9/L if baseline>20*10^9/L or increases from <20*10^9/L to >20*10^9/L and by at least 100%; neutrophil increases by 100% and absolute increases of >0.5*10^9/L if baseline <1.0*10^9/L.
measure: Number of Participants With Overall Response (OR)
time frame: From randomization until CR and PR or CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR or PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils, 0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still>5%. For low-blast AML-CR:morphologic leukemia-free state>1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but >=50% decrease in bone marrow aspirate.
measure: Number of Participants With Overall Response 2 (OR2)
time frame: From randomization until, CR, PR or HI or CR, CRi or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: OR2=participant with best overall response of CR+PR+HI in HR MDS/CMML participants,or of CR+CRi+PR in low-blast AML participants.CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100*10^9/L pl,≥1.0*10^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still >5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)<11 g/dL;pl inc≥30*10^9/L if BL>20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by 100%;neutrophil inc by 100%;absolute inc of >0.5*10^9/L if BL<100*10^9/L.For low-blast AML-CR:morphologic leukemia-free state >1.0*10^9 neutrophils,≥100*10^9/L pl,transfusion independence,no residual evidence of extramedullary leukemia;CR with incomplete blood count recovery:fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl<100*10^9/L;PR:all CR hematological values but ≥50% decrease in BM aspirate.Number of responders determined by independent review committee(IRC) assessment.
measure: Duration of Complete Remission (CR)
time frame: From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML) or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).
measure: Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)
time frame: From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). Disease responses for low-blast AML were based on the Revised IWG Response Criteria for AML. CR is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).
measure: Duration of Overall Response (OR)
time frame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR+PR for HR MDS/CMML and CR+Cri+ PR for low-blast AML.CR for HR MDS/CMML:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR:all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still >5%. For low-blast AML-CR: morphologic leukemia-free state >1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with CRi: fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but >=50% decrease in % of blasts in bone marrow aspirate.
measure: Duration of Overall Response 2 (OR2)
time frame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Duration of OR2: from date of first documentation of CR+PR+HI to first documentation of PD/relapse after CR/PR for responders of CR+PR+HI for HR MDS/CMML and CR,CRi,PR for low-blast AML. For HR MDS/CMML-CR:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb, >=100*10^9/L pl,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment, still >5%; HI:Hgb inc >=1.5 g/dL if baseline <11 g/dL; pl inc>=30*10^9/L if baseline>20*10^9/L or inc from<20*10^9/L to>20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <1.0*10^9/L.For low-blast AML-CR: morphologic leukemia-free state,>1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi: fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl <100*10^9/L;PR:all CR hematological values but>=50% decrease in bone marrow aspirate.
measure: Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence
time frame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: A participant was defined as RBC or platelet-transfusion independent if he/she received no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline.
measure: Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence
time frame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Duration of RBC and platelet transfusion independence was defined as the longest time between the last RBC and/or platelet transfusion before the start of the RBC and/or platelet transfusion-independent period and the first RBC and/or platelet transfusion after the start of the transfusion-independent period, which occurs >= 8 weeks later.
measure: Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)
time frame: From randomization until CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Time to first CR or PR is defined as the time from randomization to first documented CR or PR, whichever occurs first. Disease responses for HR MDS or CMML or low-blast AML cycle 6 are based on Modified IWG Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. For HR MDS or CMML-CR:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still>5%; For low-blast AML-CR: morphologic leukemia-free state,>1.0*10^9/L neutrophils, pl>=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
measure: Number of Participants With Hematologic Improvement (HI)
time frame: From randomization until HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase >=1.5 g/dL if baseline <11 g/dL; pl increase >=30*10^9/L if baseline >20*10^9/L or increase from <20*10^9/L to >20*10^9/L by at least 100%; neutrophil increase by 100% and absolute increase of >0.5*10^9/L if baseline <1.0*10^9/L.
measure: Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML
time frame: From randomization until transformation to AML or until initiation of subsequent therapy till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Inpatient hospital admission data was collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurred first. Transformation to AML is defined, according to WHO Classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.
measure: Time to Progressive Disease (PD), Relapse After CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death
time frame: From randomization until PD, relapse after CR, or relapse after CR or PR, or death due to any cause, whichever occurs first till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Time to PD, relapse after CR(low-blast AML), relapse after CR or PR(HR MDS/CMML), or death,defined as time from date of randomization until date of first documentation of PD,relapse after CR(low-blast AML),relapse after CR or PR(HR MDS/CMML),or death due to any cause, whichever occurs first. In HR MDS/CMML,PD: Participants with<5% blasts:>=50% inc >5% blasts, with 5%-9% blasts:>=50% inc>10% blasts, with 10%-19% blasts:>=50% inc >20% blasts,with 20%-30% blasts, at least 50% decrement from maximum remission/response in granulocytes or pl or reduction in Hgb by>=2 g/dL/new transfusion dependence.Relapse after CR or PR: return to pretreatment bone marrow blast %/Decrement of >=50% from maximum remission/response levels in granulocytes/pl/reduction in Hgb conc.>=1.5 g/dL/transfusion dependence. In AML,PD:>50% inc in bone marrow blasts to >30% blasts,>50% inc in circulating blasts to>30% blasts in peripheral blood, Development of extramedullary disease/new sites of extramedullary leukemia.
measure: Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30
time frame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
description: The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The percentage of participants for each parameter score were categorized as improved, stable, and worsened. Only categories with at least one participant with event are reported.
measure: Plasma Concentration of Pevonedistat
time frame: Cycle 1 Day 1 predose and multiple time points (up to 4 hours) post dose; Cycle 1 Days 3 and 5 predose; Cycle 2 and 4 Day 1 at multiple time points (up to 3 hours) post dose; Cycle 4 Day 3 predose (Cycle length= 28 days)
measure: Number of Participants With Overall Response in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group
time frame: From randomization until CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR + PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still>5%. For low-blast AML-CR: morphologic leukemia-free state, >1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl<100*10^9/L; PR: all CR hematological values but>=50% decrease in the percentage of blasts to 5% to 25% in bone marrow aspirate.
measure: Event-Free Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group
time frame: From randomization until transformation to AML if eligible or death till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: Event was defined as death or transformation to AML in participants with MDS or CMML, whichever occurred first. Transformation to AML was defined, according to World Health Organization (WHO) Classification as a participant having >20% blasts in the blood or marrow and increase of blast count by 50%. Event was defined as death in participants with low-blast AML.
measure: Overall Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group
time frame: From randomization until death till data cut-off date: 28 May 2021 (up to approximately 42 months)
description: OS was calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored as of the date the participant was last known to be alive.
measure: Number of Participants With Overall Response by Cycle 6
time frame: Up to Cycle 6 (up to approximately Day 168)
description: Responses for HR MDS/CMML are based on Modified International Working Group (IWG) Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR and PR for HR MDS/CMML and CR+CR with incomplete blood count recovery(CRi)+PR for low-blast AML. CR for HR MDS/CMML:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11g/dL hemoglobin (Hgb),>=100*10^9/L platelet (pl),>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood, and PR:all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%. For low-blast AML-CR:morphologic leukemia-free state,>1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia <1.0*10^9/L/thrombocytopenia (pl<100*10^9/L); PR:all CR hematological values but>=50% decrease in percentage of blasts to 5%-25% in bone marrow aspirate.
arm group label: Azacitidine 75 mg/m^2
arm group type: Experimental
description: Azacitidine 75 milligram per square meter (mg/m^2) intravenous (IV) or subcutaneous (SC) injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.
arm group label: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
arm group type: Experimental
description: Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.
intervention type: Drug
intervention name: Azacitidine
description: Azacitidine intravenous or subcutaneous formulation.
arm group label: Azacitidine 75 mg/m^2
arm group label: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
intervention type: Drug
intervention name: Pevonedistat
description: Pevonedistat intravenous infusion.
arm group label: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Takeda
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country: Australia
country: Belgium
country: Brazil
country: Canada
country: China
country: Czechia
country: France
country: Germany
country: Greece
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Mexico
country: Poland
country: Russian Federation
country: Spain
country: Turkey
country: United Kingdom
country: United States
url: https://clinicaltrials.takeda.com/study-detail/5f6b60294db2bf003ab499ea
description: Related Info
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Preleukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Leukemia, Myelomonocytic, Chronic
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Azacitidine
mesh term: Pevonedistat
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 