<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/NCT02208037</url>
  </required_header>
  <id_info>
    <org_study_id>BMTCTN1203</org_study_id>
    <secondary_id>U01HL069294</secondary_id>
    <nct_id>NCT02208037</nct_id>
  </id_info>
  <brief_title>Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN 1203)</brief_title>
  <official_title>A Multi-center Phase II Trial Randomizing Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN #1203; Progress I)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Blood and Marrow Transplant Clinical Trials Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>National Heart, Lung, and Blood Institute (NHLBI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute Graft-versus-Host-Disease (GVHD) is an important cause of morbidity and mortality after&#xD;
      allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to determine if&#xD;
      any of three new GVHD prophylaxis approaches improves the rate of GVHD and relapse free&#xD;
      survival at one year after transplant compared to the current standard prophylaxis regimen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      GVHD is a complication that can occur after a bone marrow or stem cell transplant. The&#xD;
      transplant recipient's body is attacked by the newly introduced cells. Only about 40% of&#xD;
      patients with acute GVHD have durable responses when treated with corticosteroid therapy. A&#xD;
      strategy that helps fewer people suffer from GVHD, without other adverse effects, would be an&#xD;
      effective approach to improve survival after allogeneic transplantation.&#xD;
&#xD;
      GVHD incidence can be decreased with various treatment plans. Early transplants were done&#xD;
      using post-transplant methotrexate to prevent GVHD. Another drug, cyclosporine, was later&#xD;
      shown to work better than methotrexate. Then doctors discovered that the combined use of&#xD;
      cyclosporine and methotrexate worked even better than either agent alone. More recently,&#xD;
      other calcineurin-inhibitors, such as tacrolimus have been developed as GVHD prophylactic&#xD;
      agents due to favorable toxicity profiles in comparison with cyclosporine. Studies have been&#xD;
      conducted to compare available treatment combinations for related and unrelated donors. The&#xD;
      combination of tacrolimus/methotrexate remains a standard for GVHD prophylaxis.&#xD;
&#xD;
      However, improved GVHD prophylaxis remains a significant clinical need in HSCT. The current&#xD;
      clinical trial will test three novel GVHD prophylaxis approaches: tacrolimus/methotrexate and&#xD;
      bortezomib (Tac/MTX/Bort), tacrolimus/methotrexate and maraviroc (Tac/MTX/MVC) and&#xD;
      tacrolimus/mycophenolate mofetil and cyclophosphamide (Tac/MMF/Cy). This randomized Phase II&#xD;
      clinical trial will compare each intervention arm with a Tac/MTX control.&#xD;
&#xD;
      This study will enroll people who have a cancer of the blood or lymph glands and a stem cell&#xD;
      transplant is a treatment option. The study will take at least two years and will include 270&#xD;
      participants - 90 participants in each of three treatment groups. The purpose of this study&#xD;
      is to compare three combinations of medications to see whether one or more of them are better&#xD;
      than the current standard of care (Tacrolimus/Methotrexate) to prevent GVHD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">October 2017</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>GRFS is defined as being free of grade III-IV acute GVHD onset, chronic GVHD onset requiring systemic immunosuppressive therapy, disease relapse or progression, and death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Grade II-IV Acute GVHD</measure>
    <time_frame>Day 180 Post-transplant</time_frame>
    <description>Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:&#xD;
Skin stage:&#xD;
0: No rash&#xD;
Rash &lt;25% of body surface area&#xD;
Rash on 25-50% of body surface area&#xD;
Rash on &gt; 50% of body surface area&#xD;
Generalized erythroderma with bullous formation&#xD;
Liver stage (based on bilirubin level)*:&#xD;
0: &lt;2 mg/dL&#xD;
2-3 mg/dL&#xD;
3.01-6 mg/dL&#xD;
6.01-15.0 mg/dL&#xD;
&gt;15 mg/dL&#xD;
GI stage*:&#xD;
0: No diarrhea or diarrhea &lt;500 mL/day&#xD;
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD&#xD;
Diarrhea 1000-1499 mL/day&#xD;
Diarrhea &gt;1500 mL/day&#xD;
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.&#xD;
GVHD grade:&#xD;
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Grade III-IV Acute GVHD</measure>
    <time_frame>Day 180 Post-transplant</time_frame>
    <description>Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:&#xD;
Skin stage:&#xD;
0: No rash&#xD;
Rash &lt;25% of body surface area&#xD;
Rash on 25-50% of body surface area&#xD;
Rash on &gt; 50% of body surface area&#xD;
Generalized erythroderma with bullous formation&#xD;
Liver stage (based on bilirubin level)*:&#xD;
0: &lt;2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.&gt;15 mg/dL&#xD;
GI stage*:&#xD;
0: No diarrhea or diarrhea &lt;500 mL/day&#xD;
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD&#xD;
Diarrhea 1000-1499 mL/day&#xD;
Diarrhea &gt;1500 mL/day&#xD;
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.&#xD;
GVHD grade:&#xD;
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Chronic GVHD</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. This endpoint considers the occurrence of chronic GVHD that necessitated initiation of immunosuppressive therapy for treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Relapse or Progression</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pretransplant features, or radiologic evidence of lymphoma. Progression of disease applies to patients with lymphoproliferative diseases (lymphoma or chronic lymphocytic leukemia) not in remission prior to transplantation and is defined as increase in size of prior sites of disease or evidence of new sites of disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Transplant-Related Mortality (TRM)</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>TRM is defined as death without prior disease relapse or progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease-free Survival</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>Disease-free survival is defined as being alive and free of disease relapse or progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With GVHD-free Survival</measure>
    <time_frame>1 Year Post-transplant</time_frame>
    <description>GVHD-free survival is defined as being alive without previous onset of Grade III-IV acute GVHD or chronic GVHD requiring immunosuppressive therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Overall Survival</measure>
    <time_frame>1 Year Post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Neutrophil Recovery</measure>
    <time_frame>Days 28 and 100 Post-transplant</time_frame>
    <description>Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm^3 for three consecutive measurements on three different days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Platelet Recovery</measure>
    <time_frame>Days 60 and 100 Post-transplant</time_frame>
    <description>Platelet recovery is defined as the first day of a sustained platelet count &gt;20,000/mm^3 with no platelet transfusion in the preceding seven days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Donor Cell Engraftment</measure>
    <time_frame>Days 28 and 100 Post-transplant</time_frame>
    <description>Donor cell engraftment will be assessed with donor/recipient chimerism. Chimerism may be evaluated in bone marrow, whole blood, or CD3 fractions. Full donor chimerism is defined as the presence of ≥ 95% of donor cells as a proportion of total cells. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells, of &lt; 95% but &gt; 5% in the bone marrow or peripheral blood. Full and mixed chimerism will be evidence of donor cell engraftment. Donor cells of ≤ 5% will be considered as graft rejection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary Cause of Death</measure>
    <time_frame>1 Year Post-transplant</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">279</enrollment>
  <condition>Acute Leukemia</condition>
  <condition>Chronic Myelogenous Leukemia</condition>
  <condition>Myelodysplasia</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <condition>Lymphoma, B-Cell</condition>
  <condition>Lymphoma, Follicular</condition>
  <condition>Lymphoma, Large B-Cell, Diffuse</condition>
  <condition>Hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>Tacrolimus/Methotrexate/Bortezomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tacrolimus/Methotrexate/Maraviroc</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tacrolimus/MMF/Cyclophosphamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus (ARM with Methotrexate)</intervention_name>
    <description>Tacrolimus will be given orally at a dose of 0.05 mg/kg or intravenously at a dose of 0.03 mg/kg starting Day -3. The dose of tacrolimus may be rounded to the nearest 0.5 mg for oral formulations. Subsequent dosing will be based on blood levels. The dose should be adjusted accordingly to maintain a suggested level of 5-15 ng/mL. If patients are on medications which alter the metabolism of tacrolimus (e.g. azoles), the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.</description>
    <arm_group_label>Tacrolimus/Methotrexate/Bortezomib</arm_group_label>
    <arm_group_label>Tacrolimus/Methotrexate/Maraviroc</arm_group_label>
    <other_name>Prograf®</other_name>
    <other_name>FK506</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus (ARM with MMF and Cyclophosphamide)</intervention_name>
    <description>Tacrolimus will be given orally at a dose of 0.05 mg/kg or intravenously at a dose of 0.03 mg/kg starting Day +5. Serum levels of tacrolimus will be measured at Day 7 and then should be checked weekly thereafter, and the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according to institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.</description>
    <arm_group_label>Tacrolimus/MMF/Cyclophosphamide</arm_group_label>
    <other_name>Prograf®</other_name>
    <other_name>FK506</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate (ARM with Maraviroc)</intervention_name>
    <description>Methotrexate will be administered, per institutional practices, at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate will be given at least 24 hours after the hematopoietic stem cell infusion and at least 30 minutes after the first dose of maraviroc. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices.</description>
    <arm_group_label>Tacrolimus/Methotrexate/Maraviroc</arm_group_label>
    <other_name>MTX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate (ARM with Bortezomib)</intervention_name>
    <description>Methotrexate will be administered, per institutional practices, at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate will be given at least 24 hours after the hematopoietic stem cell infusion and at least 30 minutes after the first dose of bortezomib. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices.</description>
    <arm_group_label>Tacrolimus/Methotrexate/Bortezomib</arm_group_label>
    <other_name>MTX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Maraviroc</intervention_name>
    <description>Maraviroc will be dosed at 300 mg orally twice a day and will start on Day -3 prior to hematopoietic stem cell infusion, and continue until Day 30 post HSCT. If the patient requires a two-day stem cell infusion, maraviroc treatment will end 30 days after the first infusion day.</description>
    <arm_group_label>Tacrolimus/Methotrexate/Maraviroc</arm_group_label>
    <other_name>Selzentry®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>Bortezomib will be administered at the dose of 1.3 mg/m2 based upon actual body weight (ABW) as an approximately 3-5 second IV push on Days +1, +4, and +7 after hematopoietic stem cell infusion. There must be at least 72 hours between each dose of bortezomib. Subcutaneous administration of bortezomib is not allowed on this protocol.</description>
    <arm_group_label>Tacrolimus/Methotrexate/Bortezomib</arm_group_label>
    <other_name>Velcade®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil</intervention_name>
    <description>MMF will be given at a dose of 15 mg/kg three times a day (TID) based upon ABW with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day 5 and discontinue after the last dose on Day 35, or may be continued if active GVHD is present.</description>
    <arm_group_label>Tacrolimus/MMF/Cyclophosphamide</arm_group_label>
    <other_name>Cellcept®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Hydration prior to cyclophosphamide may be given according to institutional standards.&#xD;
Mesna will be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of Mesna is equal to 80% of the total daily dose of cyclophosphamide.&#xD;
Cyclophosphamide [50 mg/kg ideal body weight (IBW); if ABW &lt; IBW, use ABW] will be given on Day 3 post-transplant (between 60 and 72 hours after the start of the HSCT) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).</description>
    <arm_group_label>Tacrolimus/MMF/Cyclophosphamide</arm_group_label>
    <other_name>Cytoxan®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-75 years (patient is older than 18.0 and less than 76.0 years old)&#xD;
&#xD;
          2. Patients with acute leukemia, chronic myelogenous leukemia or myelodysplasia with no&#xD;
             circulating blasts and with less than 5% blasts in the bone marrow.&#xD;
&#xD;
          3. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular,&#xD;
             marginal zone, diffuse large B-cell, Hodgkin's Lymphoma,or mantle cell lymphoma with&#xD;
             chemosensitive disease at time of transplantation&#xD;
&#xD;
          4. Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)&#xD;
&#xD;
          5. Patients must have a related or unrelated peripheral blood stem cell donor as follows:&#xD;
&#xD;
               1. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher)&#xD;
                  resolution, and -DRB1 at high resolution using DNA-based typing, and must be&#xD;
                  willing to donate peripheral blood stem cells and meet institutional criteria for&#xD;
                  donation.&#xD;
&#xD;
               2. Unrelated donor must be a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 at high&#xD;
                  resolution using DNA-based typing. Unrelated donor must be willing to donate&#xD;
                  peripheral blood stem cells and be medically cleared to donate stem cells&#xD;
                  according to National Marrow Donor Program (NMDP) criteria.&#xD;
&#xD;
          6. Cardiac function: Ejection fraction at rest ≥ 45%&#xD;
&#xD;
          7. Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault&#xD;
             formula and actual body weight)&#xD;
&#xD;
          8. Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 40%&#xD;
             (adjusted for hemoglobin) and forced expiratory volume in one second (FEV1) ≥ 50%&#xD;
&#xD;
          9. Liver function: total bilirubin &lt; 1.5 x the upper limit of normal and alanine&#xD;
             aminotransferase (ALT)/aspartate aminotransferase (AST) &lt; 2.5x the upper normal limit.&#xD;
             Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the&#xD;
             defined bilirubin value of 1.5x the upper limit of normal.&#xD;
&#xD;
         10. Female subjects (unless postmenopausal for at least 1 year before the screening visit,&#xD;
             or surgically sterilized), agree to practice two (2) effective methods of&#xD;
             contraception at the same time, or agree to completely abstain from heterosexual&#xD;
             intercourse, from the time of signing the informed consent through 12 months post&#xD;
             transplant (see Section 2.6.4 for definition of postmenopausal).&#xD;
&#xD;
         11. Male subjects (even if surgically sterilized), of partners of women of childbearing&#xD;
             potential must agree to one of the following: practice effective barrier contraception&#xD;
             (see Section 2.6.4 for list of barrier methods), or abstain from heterosexual&#xD;
             intercourse from the time of signing the informed consent through 12 months post&#xD;
             transplant.&#xD;
&#xD;
         12. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior allogeneic transplant&#xD;
&#xD;
          2. Karnofsky Performance Score &lt; 70%&#xD;
&#xD;
          3. Active central nervous system (CNS) involvement by malignant cells&#xD;
&#xD;
          4. Patients with uncontrolled bacterial, viral or fungal infections (currently taking&#xD;
             medication and with progression or no clinical improvement) at time of enrollment.&#xD;
&#xD;
          5. Presence of fluid collection (ascites, pleural or pericardial effusion) that&#xD;
             interferes with methotrexate clearance or makes methotrexate use contraindicated&#xD;
&#xD;
          6. Patients with transformed lymphoma (e.g., Richters transformation arising in&#xD;
             follicular lymphoma or chronic lymphocytic leukemia)&#xD;
&#xD;
          7. Patients seropositive for the human immunodeficiency virus (HIV)&#xD;
&#xD;
          8. Patient with active Hepatitis B or C determined by serology and/or nucleic acid&#xD;
             amplification tests (NAAT)&#xD;
&#xD;
          9. Patients with hypersensitivity to bortezomib, boron or mannitol&#xD;
&#xD;
         10. Patients with ≥ grade 2 sensory peripheral neuropathy&#xD;
&#xD;
         11. Myocardial infarction within 6 months prior to enrollment or New York Heart&#xD;
             Association (NYHA) Class III or IV heart failure (see Appendix D), uncontrolled&#xD;
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence&#xD;
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any&#xD;
             ECG abnormality at screening must be documented by the investigator as not medically&#xD;
             relevant.&#xD;
&#xD;
         12. Female patients who are lactating or pregnant&#xD;
&#xD;
         13. Patients with a serious medical or psychiatric illness likely to interfere with&#xD;
             participation in this clinical study&#xD;
&#xD;
         14. Patients with prior malignancies except resected basal cell carcinoma or treated&#xD;
             cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously&#xD;
             will be allowed. Cancer treated with curative intent &lt; 5 years previously will not be&#xD;
             allowed unless approved by the Protocol Officer or one of the Protocol Chairs.&#xD;
&#xD;
         15. Planned use of anti-thymocyte globulin (ATG) or alemtuzumab in conditioning regimen.&#xD;
&#xD;
         16. Planned post-transplant therapy, including use of tyrosine-kinase inhibitors (TKI).&#xD;
&#xD;
         17. Inability to withhold agents that may interact with hepatic cytochrome P450 enzymes&#xD;
             (CYP3A4), or glutathione S-transferases involved in bortezomib and/or busulfan&#xD;
             metabolism during day -5 through day +7. It is acceptable to use alternative&#xD;
             non-interacting medications during this period, and then resume prior medications.&#xD;
&#xD;
         18. Patients with secondary acute myeloid leukemia arising from myeloproliferative&#xD;
             disease, including Chronic myelomonocytic leukemia (CMML), with evidence of active&#xD;
             myeloproliferative features or myelofibrosis in the background.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mary Horowitz, MD</last_name>
    <role>Study Director</role>
    <affiliation>Center for International Blood and Marrow Transplant Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Hospital and Clinics</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine (Shands)</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33624</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BMT Program at Northside Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>22218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute/Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute/Brigham &amp; Women's</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute/BMT</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University/Barnes Jewish Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>Manhattan</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Hospital at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Cleveland/Case Western</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State/Arthur G. James Cancer Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas/MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Transplant Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Med School</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University MCV Hospitals</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23284</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bmtctn.net/</url>
    <description>Blood and Marrow Transplant Clinical Trials Network</description>
  </link>
  <link>
    <url>https://bethematch.org/</url>
    <description>National Marrow Donor Program</description>
  </link>
  <reference>
    <citation>Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.</citation>
    <PMID>7581076</PMID>
  </reference>
  <reference>
    <citation>Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.</citation>
    <PMID>16338616</PMID>
  </reference>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>August 1, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>December 4, 2018</results_first_submitted>
  <results_first_submitted_qc>January 2, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 23, 2019</results_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute Lymphoblastic Leukemia/Lymphoma</keyword>
  <keyword>Acute Myelogenous Leukemia</keyword>
  <keyword>Mantel-Cell Lymphoma</keyword>
  <keyword>Hematopoietic Transplant</keyword>
  <keyword>GVHD Prophylaxis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Maraviroc</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Within 6 months of official study closure at participating sites.</ipd_time_frame>
    <ipd_access_criteria>Available to the public</ipd_access_criteria>
    <ipd_url>https://biolincc.nhlbi.nih.gov/home/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 17, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT02208037/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>November 9, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT02208037/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tacrolimus/Methotrexate/Bortezomib</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
        </group>
        <group group_id="P2">
          <title>Tacrolimus/Methotrexate/Maraviroc</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
        </group>
        <group group_id="P3">
          <title>Tacrolimus/MMF/Cyclophosphamide</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="93"/>
                <participants group_id="P3" count="93"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="89"/>
                <participants group_id="P2" count="92"/>
                <participants group_id="P3" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tacrolimus/Methotrexate/Bortezomib</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
        </group>
        <group group_id="B2">
          <title>Tacrolimus/Methotrexate/Maraviroc</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
        </group>
        <group group_id="B3">
          <title>Tacrolimus/MMF/Cyclophosphamide</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
        </group>
        <group group_id="B4">
          <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="89"/>
            <count group_id="B2" value="92"/>
            <count group_id="B3" value="92"/>
            <count group_id="B4" value="273"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64" lower_limit="28" upper_limit="76"/>
                    <measurement group_id="B2" value="64" lower_limit="24" upper_limit="74"/>
                    <measurement group_id="B3" value="64" lower_limit="25" upper_limit="75"/>
                    <measurement group_id="B4" value="64" lower_limit="24" upper_limit="76"/>
                  </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="31"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="98"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="62"/>
                    <measurement group_id="B4" value="175"/>
                  </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="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                    <measurement group_id="B2" value="86"/>
                    <measurement group_id="B3" value="81"/>
                    <measurement group_id="B4" value="252"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="10"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="82"/>
                    <measurement group_id="B4" value="242"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HCT-CI Comorbidity Index</title>
          <description>The HCT-CI is a measure of comorbidities present in hematopoietic cell transplant patients. It is scored on an integer-valued scale from 0-29, with greater values indicating greater levels of comorbidity.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="26"/>
                    <measurement group_id="B4" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1-2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="95"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3 or greater</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="39"/>
                    <measurement group_id="B4" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Karnofsky Performance Score</title>
          <description>KPS describes patient-perceived global quality of life and functioning on a scale of 0-100.&#xD;
100: No evidence of disease; 90: Normal activity. Minor signs or symptoms of disease; 80: Normal activity with effort. Some signs or symptoms of disease; 70: Cares for self. Unable to continue normal activity; 60: Needs occasional assistance, but cares for most personal needs; 50: Needs considerable assistance and medical care; 40: Disabled. Needs special care and assistance; 30: Severely disabled. Hospital admission indicated; 20: Very sick. Active supportive therapy needed; 10: Moribund; 0: Dead</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>100</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>90</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="120"/>
                  </measurement_list>
                </category>
                <category>
                  <title>80</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="28"/>
                    <measurement group_id="B4" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>70</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HLA Matching and Donor Type</title>
          <description>For related donors, HLA matching was performed on 6 markers using HLA-A and -B at intermediate resolution and -DRB1 at high resolution. For unrelated donors, matching was performed on 8 markers using HLA-A, -B, -C and -DRB1 at high resolution.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Matched Sibling (6/6)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="91"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Matched Other Relative (6/6)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Matched Unrelated (8/8)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="50"/>
                    <measurement group_id="B4" value="151"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mismatched Unrelated (7/8)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Diagnosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Acute Myeloid Leukemia (AML)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="49"/>
                    <measurement group_id="B4" value="144"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute Lymphoblastic Leukemia (ALL)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Chronic Myelogeneous Leukemia (CML)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Chronic Lymphocytic Leukemia (CLL)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Myelodysplastic Syndrome (MDS)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Follicular Lymphoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Diffuse Large B-Cell Lymphoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mantle Cell Lymphoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hodgkin's Lymphoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time from Diagnosis to Transplant</title>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.1" lower_limit="2.1" upper_limit="110.3"/>
                    <measurement group_id="B2" value="6.3" lower_limit="2.0" upper_limit="122.5"/>
                    <measurement group_id="B3" value="7.4" lower_limit="2.1" upper_limit="139.4"/>
                    <measurement group_id="B4" value="7.1" lower_limit="2.0" upper_limit="139.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Donor/Recipient Sex Matching</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Male donor / Male Recipient</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="126"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male donor / Female Recipient</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Female donor / Male Recipient</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Female donor / Female Recipient</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Donor/Recipient Cytomegalovirus (CMV) Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Donor Positive / Recipient Positive</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="82"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Donor Positive / Recipient Negative</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Donor Negative / Recipient Positive</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="26"/>
                    <measurement group_id="B4" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Donor Negative / Recipient Negative</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)</title>
        <description>GRFS is defined as being free of grade III-IV acute GVHD onset, chronic GVHD onset requiring systemic immunosuppressive therapy, disease relapse or progression, and death from any cause.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)</title>
          <description>GRFS is defined as being free of grade III-IV acute GVHD onset, chronic GVHD onset requiring systemic immunosuppressive therapy, disease relapse or progression, and death from any cause.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.5" lower_limit="27.2" upper_limit="43.9"/>
                    <measurement group_id="O2" value="27.2" lower_limit="19.9" upper_limit="35.0"/>
                    <measurement group_id="O3" value="44.1" lower_limit="35.3" upper_limit="52.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Grade II-IV Acute GVHD</title>
        <description>Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:&#xD;
Skin stage:&#xD;
0: No rash&#xD;
Rash &lt;25% of body surface area&#xD;
Rash on 25-50% of body surface area&#xD;
Rash on &gt; 50% of body surface area&#xD;
Generalized erythroderma with bullous formation&#xD;
Liver stage (based on bilirubin level)*:&#xD;
0: &lt;2 mg/dL&#xD;
2-3 mg/dL&#xD;
3.01-6 mg/dL&#xD;
6.01-15.0 mg/dL&#xD;
&gt;15 mg/dL&#xD;
GI stage*:&#xD;
0: No diarrhea or diarrhea &lt;500 mL/day&#xD;
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD&#xD;
Diarrhea 1000-1499 mL/day&#xD;
Diarrhea &gt;1500 mL/day&#xD;
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.&#xD;
GVHD grade:&#xD;
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4</description>
        <time_frame>Day 180 Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Grade II-IV Acute GVHD</title>
          <description>Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:&#xD;
Skin stage:&#xD;
0: No rash&#xD;
Rash &lt;25% of body surface area&#xD;
Rash on 25-50% of body surface area&#xD;
Rash on &gt; 50% of body surface area&#xD;
Generalized erythroderma with bullous formation&#xD;
Liver stage (based on bilirubin level)*:&#xD;
0: &lt;2 mg/dL&#xD;
2-3 mg/dL&#xD;
3.01-6 mg/dL&#xD;
6.01-15.0 mg/dL&#xD;
&gt;15 mg/dL&#xD;
GI stage*:&#xD;
0: No diarrhea or diarrhea &lt;500 mL/day&#xD;
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD&#xD;
Diarrhea 1000-1499 mL/day&#xD;
Diarrhea &gt;1500 mL/day&#xD;
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.&#xD;
GVHD grade:&#xD;
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26" lower_limit="19" upper_limit="34"/>
                    <measurement group_id="O2" value="32" lower_limit="24" upper_limit="40"/>
                    <measurement group_id="O3" value="27" lower_limit="20" upper_limit="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Grade III-IV Acute GVHD</title>
        <description>Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:&#xD;
Skin stage:&#xD;
0: No rash&#xD;
Rash &lt;25% of body surface area&#xD;
Rash on 25-50% of body surface area&#xD;
Rash on &gt; 50% of body surface area&#xD;
Generalized erythroderma with bullous formation&#xD;
Liver stage (based on bilirubin level)*:&#xD;
0: &lt;2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.&gt;15 mg/dL&#xD;
GI stage*:&#xD;
0: No diarrhea or diarrhea &lt;500 mL/day&#xD;
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD&#xD;
Diarrhea 1000-1499 mL/day&#xD;
Diarrhea &gt;1500 mL/day&#xD;
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.&#xD;
GVHD grade:&#xD;
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4</description>
        <time_frame>Day 180 Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Grade III-IV Acute GVHD</title>
          <description>Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:&#xD;
Skin stage:&#xD;
0: No rash&#xD;
Rash &lt;25% of body surface area&#xD;
Rash on 25-50% of body surface area&#xD;
Rash on &gt; 50% of body surface area&#xD;
Generalized erythroderma with bullous formation&#xD;
Liver stage (based on bilirubin level)*:&#xD;
0: &lt;2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.&gt;15 mg/dL&#xD;
GI stage*:&#xD;
0: No diarrhea or diarrhea &lt;500 mL/day&#xD;
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD&#xD;
Diarrhea 1000-1499 mL/day&#xD;
Diarrhea &gt;1500 mL/day&#xD;
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.&#xD;
GVHD grade:&#xD;
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="4" upper_limit="13"/>
                    <measurement group_id="O2" value="9" lower_limit="4" upper_limit="14"/>
                    <measurement group_id="O3" value="2" lower_limit="0" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Chronic GVHD</title>
        <description>Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Chronic GVHD</title>
          <description>Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39" lower_limit="30" upper_limit="48"/>
                    <measurement group_id="O2" value="43" lower_limit="35" upper_limit="52"/>
                    <measurement group_id="O3" value="28" lower_limit="20" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy</title>
        <description>Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. This endpoint considers the occurrence of chronic GVHD that necessitated initiation of immunosuppressive therapy for treatment.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy</title>
          <description>Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. This endpoint considers the occurrence of chronic GVHD that necessitated initiation of immunosuppressive therapy for treatment.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29" lower_limit="22" upper_limit="38"/>
                    <measurement group_id="O2" value="33" lower_limit="25" upper_limit="41"/>
                    <measurement group_id="O3" value="22" lower_limit="15" upper_limit="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Disease Relapse or Progression</title>
        <description>Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pretransplant features, or radiologic evidence of lymphoma. Progression of disease applies to patients with lymphoproliferative diseases (lymphoma or chronic lymphocytic leukemia) not in remission prior to transplantation and is defined as increase in size of prior sites of disease or evidence of new sites of disease.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease Relapse or Progression</title>
          <description>Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pretransplant features, or radiologic evidence of lymphoma. Progression of disease applies to patients with lymphoproliferative diseases (lymphoma or chronic lymphocytic leukemia) not in remission prior to transplantation and is defined as increase in size of prior sites of disease or evidence of new sites of disease.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24" lower_limit="17" upper_limit="32"/>
                    <measurement group_id="O2" value="31" lower_limit="23" upper_limit="39"/>
                    <measurement group_id="O3" value="28" lower_limit="21" upper_limit="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Transplant-Related Mortality (TRM)</title>
        <description>TRM is defined as death without prior disease relapse or progression.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Transplant-Related Mortality (TRM)</title>
          <description>TRM is defined as death without prior disease relapse or progression.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17" lower_limit="11" upper_limit="24"/>
                    <measurement group_id="O2" value="16" lower_limit="10" upper_limit="23"/>
                    <measurement group_id="O3" value="11" lower_limit="6" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Disease-free Survival</title>
        <description>Disease-free survival is defined as being alive and free of disease relapse or progression.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease-free Survival</title>
          <description>Disease-free survival is defined as being alive and free of disease relapse or progression.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58" lower_limit="49" upper_limit="66"/>
                    <measurement group_id="O2" value="56" lower_limit="47" upper_limit="64"/>
                    <measurement group_id="O3" value="60" lower_limit="51" upper_limit="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With GVHD-free Survival</title>
        <description>GVHD-free survival is defined as being alive without previous onset of Grade III-IV acute GVHD or chronic GVHD requiring immunosuppressive therapy.</description>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With GVHD-free Survival</title>
          <description>GVHD-free survival is defined as being alive without previous onset of Grade III-IV acute GVHD or chronic GVHD requiring immunosuppressive therapy.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43" lower_limit="34" upper_limit="52"/>
                    <measurement group_id="O2" value="34" lower_limit="26" upper_limit="42"/>
                    <measurement group_id="O3" value="53" lower_limit="44" upper_limit="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Overall Survival</title>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Overall Survival</title>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68" lower_limit="59" upper_limit="76"/>
                    <measurement group_id="O2" value="66" lower_limit="57" upper_limit="74"/>
                    <measurement group_id="O3" value="71" lower_limit="63" upper_limit="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Neutrophil Recovery</title>
        <description>Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm^3 for three consecutive measurements on three different days.</description>
        <time_frame>Days 28 and 100 Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Neutrophil Recovery</title>
          <description>Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm^3 for three consecutive measurements on three different days.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94" lower_limit="89" upper_limit="98"/>
                    <measurement group_id="O2" value="93" lower_limit="89" upper_limit="97"/>
                    <measurement group_id="O3" value="95" lower_limit="90" upper_limit="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96" lower_limit="91" upper_limit="99"/>
                    <measurement group_id="O2" value="95" lower_limit="90" upper_limit="98"/>
                    <measurement group_id="O3" value="98" lower_limit="94" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Platelet Recovery</title>
        <description>Platelet recovery is defined as the first day of a sustained platelet count &gt;20,000/mm^3 with no platelet transfusion in the preceding seven days.</description>
        <time_frame>Days 60 and 100 Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Platelet Recovery</title>
          <description>Platelet recovery is defined as the first day of a sustained platelet count &gt;20,000/mm^3 with no platelet transfusion in the preceding seven days.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 60</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91" lower_limit="85" upper_limit="96"/>
                    <measurement group_id="O2" value="92" lower_limit="87" upper_limit="96"/>
                    <measurement group_id="O3" value="90" lower_limit="84" upper_limit="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91" lower_limit="85" upper_limit="96"/>
                    <measurement group_id="O2" value="92" lower_limit="87" upper_limit="96"/>
                    <measurement group_id="O3" value="96" lower_limit="91" upper_limit="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Donor Cell Engraftment</title>
        <description>Donor cell engraftment will be assessed with donor/recipient chimerism. Chimerism may be evaluated in bone marrow, whole blood, or CD3 fractions. Full donor chimerism is defined as the presence of ≥ 95% of donor cells as a proportion of total cells. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells, of &lt; 95% but &gt; 5% in the bone marrow or peripheral blood. Full and mixed chimerism will be evidence of donor cell engraftment. Donor cells of ≤ 5% will be considered as graft rejection.</description>
        <time_frame>Days 28 and 100 Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Donor Cell Engraftment</title>
          <description>Donor cell engraftment will be assessed with donor/recipient chimerism. Chimerism may be evaluated in bone marrow, whole blood, or CD3 fractions. Full donor chimerism is defined as the presence of ≥ 95% of donor cells as a proportion of total cells. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells, of &lt; 95% but &gt; 5% in the bone marrow or peripheral blood. Full and mixed chimerism will be evidence of donor cell engraftment. Donor cells of ≤ 5% will be considered as graft rejection.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 28</title>
              <category_list>
                <category>
                  <title>Full Chimerism</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="56"/>
                    <measurement group_id="O3" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mixed Chimerism</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Graft Rejection</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Dead</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Assay Performed</title>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 100</title>
              <category_list>
                <category>
                  <title>Full Chimerism</title>
                  <measurement_list>
                    <measurement group_id="O1" value="63"/>
                    <measurement group_id="O2" value="56"/>
                    <measurement group_id="O3" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mixed Chimerism</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Graft Rejection</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Dead</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Assay Performed</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Primary Cause of Death</title>
        <time_frame>1 Year Post-transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tacrolimus/Methotrexate/Bortezomib</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
          </group>
          <group group_id="O2">
            <title>Tacrolimus/Methotrexate/Maraviroc</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
          </group>
          <group group_id="O3">
            <title>Tacrolimus/MMF/Cyclophosphamide</title>
            <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Cause of Death</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="89"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Recurrence/Persistence</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute GVHD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Chronic GVHD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Infection</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Organ Failure</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hemorrhage</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Interstitial Pneumonia</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adult Respiratory Distress Syndrome</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Metastatis Breast Cancer</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Squamous Cell Carcinoma</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Toxicity - Not Specified</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Still Alive</title>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="61"/>
                    <measurement group_id="O3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 1 Year Post-transplant</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tacrolimus/Methotrexate/Bortezomib</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.</description>
        </group>
        <group group_id="E2">
          <title>Tacrolimus/Methotrexate/Maraviroc</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.</description>
        </group>
        <group group_id="E3">
          <title>Tacrolimus/MMF/Cyclophosphamide</title>
          <description>Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="30" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="93"/>
                <counts group_id="E3" subjects_affected="27" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="93"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Cardiac Arrest</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Cardiogenic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Colonic pseudo-obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Gastrointestinal perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Intestinal perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Anorectal cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Vertebral foraminal stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Guillain-Barre syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </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" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="93"/>
              </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 NOT 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>Adam Mendizabal, PhD</name_or_title>
      <organization>The Emmes Corporation</organization>
      <phone>301-251-1161</phone>
      <email>amendizabal@emmes.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/NCT02208037
org study id: BMTCTN1203
secondary id: U01HL069294
nct id: NCT02208037
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Acute Graft-versus-Host-Disease (GVHD) is an important cause of morbidity and mortality after
      allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to determine if
      any of three new GVHD prophylaxis approaches improves the rate of GVHD and relapse free
      survival at one year after transplant compared to the current standard prophylaxis regimen.
GVHD is a complication that can occur after a bone marrow or stem cell transplant. The
      transplant recipient's body is attacked by the newly introduced cells. Only about 40% of
      patients with acute GVHD have durable responses when treated with corticosteroid therapy. A
      strategy that helps fewer people suffer from GVHD, without other adverse effects, would be an
      effective approach to improve survival after allogeneic transplantation.

      GVHD incidence can be decreased with various treatment plans. Early transplants were done
      using post-transplant methotrexate to prevent GVHD. Another drug, cyclosporine, was later
      shown to work better than methotrexate. Then doctors discovered that the combined use of
      cyclosporine and methotrexate worked even better than either agent alone. More recently,
      other calcineurin-inhibitors, such as tacrolimus have been developed as GVHD prophylactic
      agents due to favorable toxicity profiles in comparison with cyclosporine. Studies have been
      conducted to compare available treatment combinations for related and unrelated donors. The
      combination of tacrolimus/methotrexate remains a standard for GVHD prophylaxis.

      However, improved GVHD prophylaxis remains a significant clinical need in HSCT. The current
      clinical trial will test three novel GVHD prophylaxis approaches: tacrolimus/methotrexate and
      bortezomib (Tac/MTX/Bort), tacrolimus/methotrexate and maraviroc (Tac/MTX/MVC) and
      tacrolimus/mycophenolate mofetil and cyclophosphamide (Tac/MMF/Cy). This randomized Phase II
      clinical trial will compare each intervention arm with a Tac/MTX control.

      This study will enroll people who have a cancer of the blood or lymph glands and a stem cell
      transplant is a treatment option. The study will take at least two years and will include 270
      participants - 90 participants in each of three treatment groups. The purpose of this study
      is to compare three combinations of medications to see whether one or more of them are better
      than the current standard of care (Tacrolimus/Methotrexate) to prevent GVHD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)
time frame: 1 Year Post-transplant
description: GRFS is defined as being free of grade III-IV acute GVHD onset, chronic GVHD onset requiring systemic immunosuppressive therapy, disease relapse or progression, and death from any cause.
measure: Percentage of Participants With Grade II-IV Acute GVHD
time frame: Day 180 Post-transplant
description: Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:
Skin stage:
0: No rash
Rash <25% of body surface area
Rash on 25-50% of body surface area
Rash on > 50% of body surface area
Generalized erythroderma with bullous formation
Liver stage (based on bilirubin level)*:
0: <2 mg/dL
2-3 mg/dL
3.01-6 mg/dL
6.01-15.0 mg/dL
>15 mg/dL
GI stage*:
0: No diarrhea or diarrhea <500 mL/day
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.
GVHD grade:
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
measure: Percentage of Participants With Grade III-IV Acute GVHD
time frame: Day 180 Post-transplant
description: Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:
Skin stage:
0: No rash
Rash <25% of body surface area
Rash on 25-50% of body surface area
Rash on > 50% of body surface area
Generalized erythroderma with bullous formation
Liver stage (based on bilirubin level)*:
0: <2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.>15 mg/dL
GI stage*:
0: No diarrhea or diarrhea <500 mL/day
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.
GVHD grade:
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
measure: Percentage of Participants With Chronic GVHD
time frame: 1 Year Post-transplant
description: Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.
measure: Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy
time frame: 1 Year Post-transplant
description: Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. This endpoint considers the occurrence of chronic GVHD that necessitated initiation of immunosuppressive therapy for treatment.
measure: Percentage of Participants With Disease Relapse or Progression
time frame: 1 Year Post-transplant
description: Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pretransplant features, or radiologic evidence of lymphoma. Progression of disease applies to patients with lymphoproliferative diseases (lymphoma or chronic lymphocytic leukemia) not in remission prior to transplantation and is defined as increase in size of prior sites of disease or evidence of new sites of disease.
measure: Percentage of Participants With Transplant-Related Mortality (TRM)
time frame: 1 Year Post-transplant
description: TRM is defined as death without prior disease relapse or progression.
measure: Percentage of Participants With Disease-free Survival
time frame: 1 Year Post-transplant
description: Disease-free survival is defined as being alive and free of disease relapse or progression.
measure: Percentage of Participants With GVHD-free Survival
time frame: 1 Year Post-transplant
description: GVHD-free survival is defined as being alive without previous onset of Grade III-IV acute GVHD or chronic GVHD requiring immunosuppressive therapy.
measure: Percentage of Participants With Overall Survival
time frame: 1 Year Post-transplant
measure: Percentage of Participants With Neutrophil Recovery
time frame: Days 28 and 100 Post-transplant
description: Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm^3 for three consecutive measurements on three different days.
measure: Percentage of Participants With Platelet Recovery
time frame: Days 60 and 100 Post-transplant
description: Platelet recovery is defined as the first day of a sustained platelet count >20,000/mm^3 with no platelet transfusion in the preceding seven days.
measure: Donor Cell Engraftment
time frame: Days 28 and 100 Post-transplant
description: Donor cell engraftment will be assessed with donor/recipient chimerism. Chimerism may be evaluated in bone marrow, whole blood, or CD3 fractions. Full donor chimerism is defined as the presence of ≥ 95% of donor cells as a proportion of total cells. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells, of < 95% but > 5% in the bone marrow or peripheral blood. Full and mixed chimerism will be evidence of donor cell engraftment. Donor cells of ≤ 5% will be considered as graft rejection.
measure: Primary Cause of Death
time frame: 1 Year Post-transplant
arm group label: Tacrolimus/Methotrexate/Bortezomib
arm group type: Experimental
description: Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Bortezomib.
arm group label: Tacrolimus/Methotrexate/Maraviroc
arm group type: Experimental
description: Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Maraviroc.
arm group label: Tacrolimus/MMF/Cyclophosphamide
arm group type: Experimental
description: Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
intervention type: Drug
intervention name: Tacrolimus (ARM with Methotrexate)
description: Tacrolimus will be given orally at a dose of 0.05 mg/kg or intravenously at a dose of 0.03 mg/kg starting Day -3. The dose of tacrolimus may be rounded to the nearest 0.5 mg for oral formulations. Subsequent dosing will be based on blood levels. The dose should be adjusted accordingly to maintain a suggested level of 5-15 ng/mL. If patients are on medications which alter the metabolism of tacrolimus (e.g. azoles), the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.
arm group label: Tacrolimus/Methotrexate/Bortezomib
arm group label: Tacrolimus/Methotrexate/Maraviroc
other name: Prograf®
other name: FK506
intervention type: Drug
intervention name: Tacrolimus (ARM with MMF and Cyclophosphamide)
description: Tacrolimus will be given orally at a dose of 0.05 mg/kg or intravenously at a dose of 0.03 mg/kg starting Day +5. Serum levels of tacrolimus will be measured at Day 7 and then should be checked weekly thereafter, and the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according to institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.
arm group label: Tacrolimus/MMF/Cyclophosphamide
other name: Prograf®
other name: FK506
intervention type: Drug
intervention name: Methotrexate (ARM with Maraviroc)
description: Methotrexate will be administered, per institutional practices, at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate will be given at least 24 hours after the hematopoietic stem cell infusion and at least 30 minutes after the first dose of maraviroc. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices.
arm group label: Tacrolimus/Methotrexate/Maraviroc
other name: MTX
intervention type: Drug
intervention name: Methotrexate (ARM with Bortezomib)
description: Methotrexate will be administered, per institutional practices, at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate will be given at least 24 hours after the hematopoietic stem cell infusion and at least 30 minutes after the first dose of bortezomib. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices.
arm group label: Tacrolimus/Methotrexate/Bortezomib
other name: MTX
intervention type: Drug
intervention name: Maraviroc
description: Maraviroc will be dosed at 300 mg orally twice a day and will start on Day -3 prior to hematopoietic stem cell infusion, and continue until Day 30 post HSCT. If the patient requires a two-day stem cell infusion, maraviroc treatment will end 30 days after the first infusion day.
arm group label: Tacrolimus/Methotrexate/Maraviroc
other name: Selzentry®
intervention type: Drug
intervention name: Bortezomib
description: Bortezomib will be administered at the dose of 1.3 mg/m2 based upon actual body weight (ABW) as an approximately 3-5 second IV push on Days +1, +4, and +7 after hematopoietic stem cell infusion. There must be at least 72 hours between each dose of bortezomib. Subcutaneous administration of bortezomib is not allowed on this protocol.
arm group label: Tacrolimus/Methotrexate/Bortezomib
other name: Velcade®
intervention type: Drug
intervention name: Mycophenolate mofetil
description: MMF will be given at a dose of 15 mg/kg three times a day (TID) based upon ABW with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day 5 and discontinue after the last dose on Day 35, or may be continued if active GVHD is present.
arm group label: Tacrolimus/MMF/Cyclophosphamide
other name: Cellcept®
intervention type: Drug
intervention name: Cyclophosphamide
description: Hydration prior to cyclophosphamide may be given according to institutional standards.
Mesna will be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of Mesna is equal to 80% of the total daily dose of cyclophosphamide.
Cyclophosphamide [50 mg/kg ideal body weight (IBW); if ABW < IBW, use ABW] will be given on Day 3 post-transplant (between 60 and 72 hours after the start of the HSCT) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).
arm group label: Tacrolimus/MMF/Cyclophosphamide
other name: Cytoxan®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Mary Horowitz, MD
role: Study Director
affiliation: Center for International Blood and Marrow Transplant Research
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country: United States
url: http://www.bmtctn.net/
description: Blood and Marrow Transplant Clinical Trials Network
url: https://bethematch.org/
description: National Marrow Donor Program
citation: Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
PMID: 7581076
citation: Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
PMID: 16338616
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Lymphoma, Follicular
mesh term: Graft vs Host Disease
mesh term: Mycophenolic Acid
mesh term: Maraviroc
mesh term: Cyclophosphamide
mesh term: Methotrexate
mesh term: Bortezomib
mesh term: Tacrolimus
sharing ipd: Yes
ipd description: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).
ipd info type: Study Protocol
ipd time frame: Within 6 months of official study closure at participating sites.
ipd access criteria: Available to the public
ipd url: https://biolincc.nhlbi.nih.gov/home/
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 