<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/NCT01690520</url>
  </required_header>
  <id_info>
    <org_study_id>2603.00</org_study_id>
    <secondary_id>NCI-2012-01572</secondary_id>
    <secondary_id>2603</secondary_id>
    <secondary_id>2603.00</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>P50HL110787</secondary_id>
    <nct_id>NCT01690520</nct_id>
  </id_info>
  <brief_title>Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes</brief_title>
  <official_title>Multi-Center, Open-Label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-The-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells in Patients With Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nohla Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Nohla Therapeutics, Inc.</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>
      This randomized phase II trial studies how well donor umbilical cord blood transplant with or&#xD;
      without ex-vivo expanded cord blood progenitor cells works in treating patients with acute&#xD;
      myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or&#xD;
      myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor&#xD;
      umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the&#xD;
      patient's immune system from rejecting the donor's cells. When the healthy stem cells and&#xD;
      ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the&#xD;
      patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It&#xD;
      is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded&#xD;
      cord blood progenitor cells is more effective than giving a donor umbilical cord blood&#xD;
      transplant alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] &gt;= 500) in&#xD;
      patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented&#xD;
      with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not&#xD;
      receive the product.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Provide initial data on clinical and economic benefit, such as time to platelet&#xD;
      engraftment, duration of initial hospitalization, transplant-related mortality (TRM), death&#xD;
      without engraftment, and incidence of severe infections in the first 100 days&#xD;
      post-transplant.&#xD;
&#xD;
      II. The kinetics of immune system recovery will also be evaluated in both arms.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      Standard of Care Arm:&#xD;
&#xD;
      CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending&#xD;
      physician: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days&#xD;
      -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose total-body irradiation&#xD;
      (TBI) twice daily (BID) on days -4 to -1 OR, patients receive fludarabine phosphate IV over&#xD;
      30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on&#xD;
      days -5 to -4, and undergo middle intensity TBI once daily (QD) on days -2 to -1.&#xD;
&#xD;
      TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood&#xD;
      (UCB) transplant on day 0.&#xD;
&#xD;
      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour&#xD;
      BID (adults) or thrice daily (TID) (children) or orally (PO) on days -3 to 100 with taper&#xD;
      beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7&#xD;
      then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then&#xD;
      may begin taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
&#xD;
      Experimental Arm:&#xD;
&#xD;
      CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending&#xD;
      physician as in Standard of Care Arm.&#xD;
&#xD;
      TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day&#xD;
      0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4&#xD;
      hours after completion of UCB transplant.&#xD;
&#xD;
      GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO&#xD;
      as in Standard of Care Arm.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 11, 2012</start_date>
  <completion_date type="Actual">May 29, 2020</completion_date>
  <primary_completion_date type="Actual">September 18, 2018</primary_completion_date>
  <phase>Phase 2</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>Time to Neutrophil Engraftment</measure>
    <time_frame>Up to 55 days post-transplant</time_frame>
    <description>First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Platelet Engraftment (20k)</measure>
    <time_frame>Up to 100 days post-transplant</time_frame>
    <description>First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse Mortality</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients With Severe Acute Graft Versus Host Disease</measure>
    <time_frame>Up to 100 days post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Chronic Graft Versus Host Disease</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">163</enrollment>
  <condition>Acute Biphenotypic Leukemia</condition>
  <condition>Acute Lymphoblastic Leukemia in Remission</condition>
  <condition>Acute Myeloid Leukemia in Remission</condition>
  <condition>Chronic Myelogenous Leukemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <arm_group>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (experimental)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclosporine</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (experimental)</arm_group_label>
    <other_name>NLA101</other_name>
    <other_name>Dilanubicel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiotepa</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total-Body Irradiation</intervention_name>
    <description>Undergo high dose or middle intensity TBI</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Umbilical Cord Blood Transplantation</intervention_name>
    <description>Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
    <arm_group_label>Arm I (standard of care)</arm_group_label>
    <arm_group_label>Arm II (experimental)</arm_group_label>
    <other_name>Cord Blood Transplantation</other_name>
    <other_name>UCB transplantation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age criteria:&#xD;
&#xD;
               -  High dose TBI regimen: 6 months to =&lt; 45 years&#xD;
&#xD;
               -  Middle intensity TBI regimen: 6 months to =&lt; 65 years&#xD;
&#xD;
               -  Conditioning regimen selection should be based on the underlying disease,&#xD;
                  presence of minimal residual disease (MRD), age, co-morbidities, attending&#xD;
                  physician, and site preference; conditioning regimen will not require&#xD;
                  stratification of the randomization due to heterogeneity in the cohort of&#xD;
                  eligible patients.&#xD;
&#xD;
          -  Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage&#xD;
             leukemia&#xD;
&#xD;
               -  All patients must have acute myeloid leukemia (AML) that is considered best&#xD;
                  treated by stem cell transplant by the referring physician and the attending&#xD;
                  transplant physician&#xD;
&#xD;
               -  All patients must be in complete remission (CR) as defined by &lt; 5% blasts by&#xD;
                  morphology/flow cytometry in a representative bone marrow sample with cellularity&#xD;
                  &gt;= 15% for age&#xD;
&#xD;
               -  Patients in which adequate marrow/biopsy specimens cannot be obtained to&#xD;
                  determine remission status by morphologic assessment, but have fulfilled criteria&#xD;
                  of remission by flow cytometry, recovery of peripheral blood counts with no&#xD;
                  circulating blasts, and/or normal cytogenetics (if applicable) may still be&#xD;
                  eligible; reasonable attempts must be made to obtain an adequate specimen for&#xD;
                  morphologic assessment, including possible repeat procedures; these patients must&#xD;
                  be discussed with the principal investigator prior to enrollment&#xD;
&#xD;
          -  Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage&#xD;
             leukemia&#xD;
&#xD;
               -  High risk first complete remission (CR1) (for example, but not limited to:&#xD;
                  t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements,&#xD;
                  hypodiploid); or high risk (HR) as defined by referring institution treatment&#xD;
                  protocol greater than 1 cycle to obtain CR; second complete remission (CR2) or&#xD;
                  greater&#xD;
&#xD;
               -  All patients must be in CR as defined by &lt; 5% blasts by morphology/flow cytometry&#xD;
                  in a representative bone marrow sample with cellularity &gt;= 15% for age&#xD;
&#xD;
               -  Patients in which adequate marrow/biopsy specimens cannot be obtained to&#xD;
                  determine remission status by morphologic assessment, but have fulfilled criteria&#xD;
                  of remission by flow cytometry, recovery of peripheral blood counts with no&#xD;
                  circulating blasts, and/or normal cytogenetics (if applicable) may still be&#xD;
                  eligible; reasonable attempts must be made to obtain an adequate specimen for&#xD;
                  morphologic assessment, including possible repeat procedures; these patients must&#xD;
                  be discussed with the principal investigator prior to enrollment&#xD;
&#xD;
          -  Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in&#xD;
             first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase&#xD;
             inhibitor therapy&#xD;
&#xD;
          -  Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate&#xD;
             (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], refractory&#xD;
             anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe&#xD;
             pancytopenia or high risk cytogenetics; blasts must be &lt; 10% by a representative bone&#xD;
             marrow aspirate morphology&#xD;
&#xD;
          -  Karnofsky (&gt;= 16 years old) &gt;= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1&#xD;
&#xD;
          -  Lansky (&lt; 16 years old) &gt;= 60&#xD;
&#xD;
          -  Adults: calculated creatinine clearance must be &gt; 60 mL and serum creatinine =&lt; 2&#xD;
             mg/dL&#xD;
&#xD;
          -  Children (&lt; 18 years old): calculated creatinine clearance must be &gt; 60 mL/min&#xD;
&#xD;
          -  Total serum bilirubin must be &lt; 3 mg/dL unless the elevation is thought to be due to&#xD;
             Gilbert's disease or hemolysis&#xD;
&#xD;
          -  Transaminases must be &lt; 3 x the upper limit of normal per reference values of&#xD;
             referring institution&#xD;
&#xD;
          -  Diffusing capacity of the lung for carbon monoxide (DLCO) corrected &gt; 60% normal&#xD;
&#xD;
          -  For pediatric patients unable to perform pulmonary function tests, oxygen (O2)&#xD;
             saturation &gt; 92% on room air&#xD;
&#xD;
          -  May not be on supplemental oxygen&#xD;
&#xD;
          -  Left ventricular ejection fraction &gt; 45% OR&#xD;
&#xD;
          -  Shortening fraction &gt; 26%&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled viral or bacterial infection at the time of study enrollment&#xD;
&#xD;
          -  Active or recent (prior 6 month) invasive fungal infection without infectious disease&#xD;
             (ID) consult and approval&#xD;
&#xD;
          -  History of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Prior myeloablative transplant containing full dose TBI (greater than 8 Gy)&#xD;
&#xD;
          -  Central nervous system (CNS) leukemic involvement not clearing with intrathecal&#xD;
             chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic&#xD;
             lumbar puncture is to be performed per protocol&#xD;
&#xD;
          -  Patients &gt;= 45 years: comorbidity score of 5 or higher&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Filippo Milano</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Cancer Institute Palo Alto</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80217-3364</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>March 26, 2021</results_first_submitted>
  <results_first_submitted_qc>June 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 6, 2021</results_first_posted>
  <last_update_submitted>June 13, 2021</last_update_submitted>
  <last_update_submitted_qc>June 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Biphenotypic, Acute</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>Cyclosporine</mesh_term>
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Thiotepa</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Cyclosporins</mesh_term>
  </intervention_browse>
  <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>March 27, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT01690520/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>February 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT01690520/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The Full Analysis Set includes all randomized subjects (78 in Arm I SOC and 82 in Arm II Expanded Arm). The modified intent to treat (mITT) analysis set requires subjects in the FAS to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug and are therefore not included in the mITT analysis set (78 in SOC and 80 in Expanded Arm).</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Standard of Care)</title>
          <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Experimental)</title>
          <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="82"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Modified Intent to Treat (mITT)</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Relapse</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing Follow-Up at time of Analysis</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm I (Standard of Care)</title>
          <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
        </group>
        <group group_id="B2">
          <title>Arm II (Experimental)</title>
          <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</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="78"/>
            <count group_id="B2" value="82"/>
            <count group_id="B3" value="160"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="109"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.76" spread="14.858"/>
                    <measurement group_id="B2" value="27.72" spread="14.699"/>
                    <measurement group_id="B3" value="27.25" spread="14.738"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="93"/>
                  </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>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="57"/>
                    <measurement group_id="B3" value="116"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                  </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>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="86"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height (cm)</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="160.09" spread="23.481"/>
                    <measurement group_id="B2" value="159.85" spread="24.680"/>
                    <measurement group_id="B3" value="159.97" spread="24.028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67.70" spread="26.886"/>
                    <measurement group_id="B2" value="69.77" spread="27.103"/>
                    <measurement group_id="B3" value="68.76" spread="26.933"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cord Blood Units Received</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>1 Cord Blood Unit</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2 Cord Blood Units</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to Neutrophil Engraftment</title>
        <description>First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.</description>
        <time_frame>Up to 55 days post-transplant</time_frame>
        <population>The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Standard of Care)</title>
            <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Experimental)</title>
            <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Neutrophil Engraftment</title>
          <description>First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.</description>
          <population>The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.</population>
          <units>days</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="72"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" lower_limit="19.0" upper_limit="22.0"/>
                    <measurement group_id="O2" value="22.0" lower_limit="20.0" upper_limit="24.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Platelet Engraftment (20k)</title>
        <description>First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.</description>
        <time_frame>Up to 100 days post-transplant</time_frame>
        <population>The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Standard of Care)</title>
            <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Experimental)</title>
            <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Platelet Engraftment (20k)</title>
          <description>First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.</description>
          <population>The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.</population>
          <units>days</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="65"/>
                <count group_id="O2" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0" lower_limit="34.0" upper_limit="42.0"/>
                    <measurement group_id="O2" value="38.0" lower_limit="35.0" upper_limit="43.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Standard of Care)</title>
            <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Experimental)</title>
            <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                    <measurement group_id="O2" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Non-relapse Mortality</title>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Standard of Care)</title>
            <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Experimental)</title>
            <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
        </group_list>
        <measure>
          <title>Non-relapse Mortality</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients With Severe Acute Graft Versus Host Disease</title>
        <time_frame>Up to 100 days post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Standard of Care)</title>
            <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Experimental)</title>
            <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients With Severe Acute Graft Versus Host Disease</title>
          <units>proportion 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="78"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.14" lower_limit="0.07" upper_limit="0.24"/>
                    <measurement group_id="O2" value="0.16" lower_limit="0.09" upper_limit="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Chronic Graft Versus Host Disease</title>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Standard of Care)</title>
            <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Experimental)</title>
            <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Chronic Graft Versus Host Disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>84 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm I (Standard of Care)</title>
          <description>CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
        </group>
        <group group_id="E2">
          <title>Arm II (Experimental)</title>
          <description>CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.&#xD;
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.&#xD;
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.&#xD;
Cyclophosphamide: Given IV&#xD;
Cyclosporine: Given IV or PO&#xD;
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV&#xD;
Fludarabine Phosphate: Given IV&#xD;
Mycophenolate Mofetil: Given IV or PO&#xD;
Thiotepa: Given IV&#xD;
Total-Body Irradiation: Undergo high dose or middle intensity TBI&#xD;
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant</description>
        </group>
      </group_list>
      <serious_events>
        <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="25" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="55" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Disseminated intravascular coagulation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lymphatic disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Jejunal perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumatosis intestinalis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Complication associated with device</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Acute graft versus host disease in intestine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Graft versus host disease in gastrointestinal tract</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Acute graft versus host disease in liver</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Graft versus host disease</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Herpes virus infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Klebsiella infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Oral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumonia klebsiella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pseudomonas infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Systemic candida</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urinary tract infection enterococcal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>BK virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus viraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumonia fungal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Transplant failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Posterior reversible encephalopathy syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Organising pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pulmonary alveolar haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pulmonary infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pulmonary mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="71" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="73" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemolytic uraemic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Thrombotic microangiopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Thrombotic thrombocytopenic purpura</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Haemolysis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Large intestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Impaired gastric emptying</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Periodontal disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumatosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Graft versus host disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Enterococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Adenovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Alpha haemolytic streptococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>BK virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Escherichia infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Human polyomavirus infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pseudomonas infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Stomatococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Actinomycotic sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Administration site cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Bacillus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Coronavirus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Corynebacterium infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Enterobacter infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Enterocolitis infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Escherichia bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Fusobacterium infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Gastric infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Leuconostoc infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Human herpesvirus 6 infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cytomegalovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Streptococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Tracheal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Blood aluminium increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urine output decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </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="39" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="38" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Acidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypermagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Iron overload</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dysaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Myoclonus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Vulvovaginal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pharyngeal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Organising pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Stridor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="82"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="82"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="78"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="82"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Scientific Officer</name_or_title>
      <organization>Deverra Therapeutics</organization>
      <phone>206-519-5304</phone>
      <email>cdelaney@deverratx.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/NCT01690520
org study id: 2603.00
secondary id: NCI-2012-01572
secondary id: 2603
secondary id: 2603.00
secondary id: P30CA015704
secondary id: P50HL110787
nct id: NCT01690520
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase II trial studies how well donor umbilical cord blood transplant with or
      without ex-vivo expanded cord blood progenitor cells works in treating patients with acute
      myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or
      myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor
      umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the
      patient's immune system from rejecting the donor's cells. When the healthy stem cells and
      ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the
      patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It
      is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded
      cord blood progenitor cells is more effective than giving a donor umbilical cord blood
      transplant alone.
PRIMARY OBJECTIVES:

      I. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] >= 500) in
      patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented
      with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not
      receive the product.

      SECONDARY OBJECTIVES:

      I. Provide initial data on clinical and economic benefit, such as time to platelet
      engraftment, duration of initial hospitalization, transplant-related mortality (TRM), death
      without engraftment, and incidence of severe infections in the first 100 days
      post-transplant.

      II. The kinetics of immune system recovery will also be evaluated in both arms.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      Standard of Care Arm:

      CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending
      physician: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days
      -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose total-body irradiation
      (TBI) twice daily (BID) on days -4 to -1 OR, patients receive fludarabine phosphate IV over
      30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on
      days -5 to -4, and undergo middle intensity TBI once daily (QD) on days -2 to -1.

      TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood
      (UCB) transplant on day 0.

      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour
      BID (adults) or thrice daily (TID) (children) or orally (PO) on days -3 to 100 with taper
      beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7
      then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then
      may begin taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

      Experimental Arm:

      CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending
      physician as in Standard of Care Arm.

      TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day
      0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4
      hours after completion of UCB transplant.

      GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO
      as in Standard of Care Arm.

      After completion of study treatment, patients are followed up periodically for 2 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to Neutrophil Engraftment
time frame: Up to 55 days post-transplant
description: First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.
measure: Time to Platelet Engraftment (20k)
time frame: Up to 100 days post-transplant
description: First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.
measure: Overall Survival
time frame: Up to 2 years
measure: Non-relapse Mortality
time frame: Up to 2 years
measure: Proportion of Patients With Severe Acute Graft Versus Host Disease
time frame: Up to 100 days post-transplant
measure: Proportion of Participants With Chronic Graft Versus Host Disease
time frame: Up to 2 years
arm group label: Arm I (standard of care)
arm group type: Active Comparator
description: CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
arm group label: Arm II (experimental)
arm group type: Experimental
description: CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
intervention type: Drug
intervention name: Cyclosporine
description: Given IV or PO
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
intervention type: Biological
intervention name: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion
description: Given IV
arm group label: Arm II (experimental)
other name: NLA101
other name: Dilanubicel
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Given IV or PO
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
intervention type: Drug
intervention name: Thiotepa
description: Given IV
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
intervention type: Radiation
intervention name: Total-Body Irradiation
description: Undergo high dose or middle intensity TBI
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
intervention type: Procedure
intervention name: Umbilical Cord Blood Transplantation
description: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
arm group label: Arm I (standard of care)
arm group label: Arm II (experimental)
other name: Cord Blood Transplantation
other name: UCB transplantation
criteria: 
gender: All
minimum age: 6 Months
maximum age: 65 Years
healthy volunteers: No
last name: Filippo Milano
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Biphenotypic, Acute
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Cyclosporine
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Thiotepa
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Cyclosporins
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 