<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/NCT04484363</url>
  </required_header>
  <id_info>
    <org_study_id>Pevonedistat-5005</org_study_id>
    <nct_id>NCT04484363</nct_id>
  </id_info>
  <brief_title>Expanded Access Program With Pevonedistat (Given With Azacitidine) for Adults With Higher-risk Myelodysplastic Syndromes</brief_title>
  <official_title>Expanded Access Program: Pevonedistat (in Combination With Azacitidine) for the First-line Treatment of Higher Risk Myelodysplastic Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <brief_summary>
    <textblock>
      Participants in the expanded access program are adults with higher-risk myelodysplastic&#xD;
      syndromes who have no other treatment options available.&#xD;
&#xD;
      The main aim of this program is to allow participants to have access to pevonedistat before&#xD;
      FDA approval.&#xD;
&#xD;
      This program will take place in the United States.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an expanded access program in which the drug being tested is called pevonedistat,&#xD;
      which is used in combination with azcitidine. This study will provide expanded access of&#xD;
      pevonedistat (in combination with azacitidine) for the first-line treatment to participants&#xD;
      with HR-MDS and option of real world data (RWD) collection for the benefit of future&#xD;
      participants.&#xD;
&#xD;
      All participants will receive azacitidine via intravenous or subcutaneous route in&#xD;
      combination with pevonedistat intravenous infusion.&#xD;
&#xD;
      This multi-center trial will be conducted in the United States. Participant will continue&#xD;
      treatment until benefit is no longer derived from the treatment (that is, until disease&#xD;
      progression, or treatment is no longer tolerable), the benefit-risk no longer favors the&#xD;
      individual, an appropriate alternative therapy becomes available, the participant chooses to&#xD;
      discontinue the treatment, or pevonedistat becomes commercially available.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>No longer available</overall_status>
  <study_type>Expanded Access</study_type>
  <has_expanded_access>No</has_expanded_access>
  <expanded_access_info>
    <expanded_access_type_intermediate>Yes</expanded_access_type_intermediate>
  </expanded_access_info>
  <condition>Myelodysplastic Syndromes</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pevonedistat</intervention_name>
    <description>Pevonedistat 20 milligram per square meter (mg/m^2), intravenous infusion, on Days 1, 3, and 5 of repeated 28-day cycles.</description>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>Azacitidine 75 mg/m^2, intravenous or subcutaneous infusion, on Days 1 to 5, Days 8 and 9 of repeated 28-day cycles or Days 1 through 7 of repeated 28-day cycles.</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has morphologically confirmed diagnosis of MDS.&#xD;
&#xD;
          2. With MDS have one of the following Prognostic Risk Categories, based on the Revised&#xD;
             International Prognostic Scoring System (IPSS-R)&#xD;
&#xD;
               -  Very high (greater than [&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 greater than or&#xD;
                  equal to (&gt;=) 5 percent (%) bone marrow myeloblasts.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2.&#xD;
&#xD;
          4. Has never been treated with Azacitidine, or, has been treated with Azacitidine, two or&#xD;
             fewer cycles of Azacitidine have been administered, and has not relapsed while being&#xD;
             treated with Azacitidine or failed Azacitidine treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has previous treatment for HR MDS with chemotherapy or other antineoplastic agents&#xD;
             including hypomethylating agent (HMAs) such as decitabine or more than two cycles of&#xD;
             azacitidine.&#xD;
&#xD;
             • Previous treatment with lenalidomide is permitted, except that lenalidomide may not&#xD;
             be given within 8 weeks of first dose of 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. Has either clinical evidence of or history of central nervous system involvement by&#xD;
             acute myelogenous leukemia (AML).&#xD;
&#xD;
          4. Active uncontrolled infection or severe infectious disease, such as severe pneumonia,&#xD;
             meningitis, or septicemia.&#xD;
&#xD;
          5. Has prothrombin time (PT) or activated partial thromboplastin time (aPTT) &gt;1.5*upper&#xD;
             limit of normal (ULN) or active uncontrolled coagulopathy or bleeding disorder.&#xD;
             Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors,&#xD;
             direct factor Xa inhibitors, or heparin are excluded from enrollment.&#xD;
&#xD;
          6. Has known hepatitis B surface antigen seropositivity, or known or suspected active&#xD;
             hepatitis C infection. Note: Participants who have isolated positive hepatitis B core&#xD;
             antibody (that is, 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;
             Participants who have positive hepatitis C antibody may be included if they have an&#xD;
             undetectable hepatitis C viral load.&#xD;
&#xD;
          7. Has known hepatic cirrhosis or severe preexisting hepatic impairment.&#xD;
&#xD;
          8. 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;
          9. Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the&#xD;
             first dose of pevonedistat.&#xD;
&#xD;
             .&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f6b603d4db2bf003ab4a3be</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</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>Preleukemia</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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04484363
org study id: Pevonedistat-5005
nct id: NCT04484363
lead sponsor: 
Participants in the expanded access program are adults with higher-risk myelodysplastic
      syndromes who have no other treatment options available.

      The main aim of this program is to allow participants to have access to pevonedistat before
      FDA approval.

      This program will take place in the United States.
This is an expanded access program in which the drug being tested is called pevonedistat,
      which is used in combination with azcitidine. This study will provide expanded access of
      pevonedistat (in combination with azacitidine) for the first-line treatment to participants
      with HR-MDS and option of real world data (RWD) collection for the benefit of future
      participants.

      All participants will receive azacitidine via intravenous or subcutaneous route in
      combination with pevonedistat intravenous infusion.

      This multi-center trial will be conducted in the United States. Participant will continue
      treatment until benefit is no longer derived from the treatment (that is, until disease
      progression, or treatment is no longer tolerable), the benefit-risk no longer favors the
      individual, an appropriate alternative therapy becomes available, the participant chooses to
      discontinue the treatment, or pevonedistat becomes commercially available.
expanded access type intermediate: Yes
intervention type: Drug
intervention name: Pevonedistat
description: Pevonedistat 20 milligram per square meter (mg/m^2), intravenous infusion, on Days 1, 3, and 5 of repeated 28-day cycles.
intervention type: Drug
intervention name: Azacitidine
description: Azacitidine 75 mg/m^2, intravenous or subcutaneous infusion, on Days 1 to 5, Days 8 and 9 of repeated 28-day cycles or Days 1 through 7 of repeated 28-day cycles.
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Study Director
role: Study Director
affiliation: Takeda
url: https://clinicaltrials.takeda.com/study-detail/5f6b603d4db2bf003ab4a3be
description: Related Info
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Azacitidine
mesh term: Pevonedistat