xml: <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/NCT06001385</url>
    </required_header>
    <id_info>
      <org_study_id>OPTIMIZE</org_study_id>
      <nct_id>NCT06001385</nct_id>
    </id_info>
    <brief_title>HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis</brief_title>
    <acronym>OPTIMIZE</acronym>
    <official_title>A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Center for International Blood and Marrow Transplant Research</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Marrow Donor Program</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Center for International Blood and Marrow Transplant Research</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to determine the effectiveness of Reduced Dose&#xD;
        Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after&#xD;
        receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question[s] it aims to answer&#xD;
        are:&#xD;
  &#xD;
          -  Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days&#xD;
             after transplant?&#xD;
  &#xD;
          -  Does a reduced dose of PTCy maintain the same level of protection against Graft Versus&#xD;
             Host Disease (GvHD) as the standard dose of PTCy?&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">February 1, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Infection Free Survival</measure>
      <time_frame>100 days post-HCT</time_frame>
      <description>Survival at 100 days without grades 2-3 infections (per BMT CTN grading criteria)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as time interval between date of transplant and death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as disease relapse or progression, or death by any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infection-free survival</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as death and grades II-III infection (per BMT CTN criteria)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Graft versus host disease relapse free survival</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as relapse or progression of underling disease (by 1 year), grade III-IV acute GvHD (by 6 months), chronic GvHD requiring systemic immune suppression (by 1 year), or death by any cause (by 1 year).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Non-relapse mortality</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as death without evidence of disease progression or recurrence</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of neutrophil recovery</measure>
      <time_frame>Day 28 post-HCT</time_frame>
      <description>Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of platelet recovery</measure>
      <time_frame>Day 28 post-HCT</time_frame>
      <description>Defined as platelet count ≥20,000/mm^3 or ≥50,000/mm^3 with no platelet transfusions within seven days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of primary and secondary graft failure</measure>
      <time_frame>Day 28 and 1-year post-HCT</time_frame>
      <description>Primary graft failure is defined as no neutrophil recovery to ≥ 500 cells/mm3 by Day 28 post HCT.&#xD;
  Secondary graft failure is defined as as initial neutrophil count recovery followed by subsequent decline in absolute neutrophil counts &lt;500 cells/mm3, unresponsive to growth factor therapy, but cannot be explained by infection, disease relapse, or medications.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Donor T-Cell Chimerism</measure>
      <time_frame>Day 28, 100 and 365 post-HCT</time_frame>
      <description>Defined as percent of donor chimerism via peripheral blood</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of acute GvHD</measure>
      <time_frame>Day 100 and Day 180 post-HCT</time_frame>
      <description>Defined as cumulative incidence of grades II-IV acute GvHD</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of chronic GvHD</measure>
      <time_frame>1-year post-HCT</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of grade 2-3 bacterial, fungal, and viral infections</measure>
      <time_frame>Day 100 and 1-year post-HCT</time_frame>
      <description>Defined as grades 2-3 infection as defined by BMT CTN grading criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of grades 2-3 BK virus hemorrhagic cystitis</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as incidence of BK virus hemorrhagic cystitis per BMT CTN grading criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of relapse/progression</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>Defined as disease relapse or progression from Day 0 to 1-year post-HCT</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Toxicity</measure>
      <time_frame>1-year post-HCT</time_frame>
      <description>To tabulate adverse events (AEs, experienced by recipients, defined as grade 3-5 unexpected and grade 5 expected AEs according to CTCAE v5</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and Severity of cytokine release syndrome</measure>
      <time_frame>within 14 days post-HCT</time_frame>
      <description>Defined and graded using the ASTCT grading criteria.</description>
    </secondary_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Anticipated">170</enrollment>
    <condition>Acute Lymphoblastic Leukemia</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Acute Leukemia</condition>
    <condition>Myelodysplastic Syndromes</condition>
    <condition>Chronic Myeloid Leukemia</condition>
    <condition>Chronic Lymphocytic Leukemia</condition>
    <condition>Myeloproliferative Neoplasm</condition>
    <condition>Lymphoma</condition>
    <condition>Chronic Myelomonocytic Leukemia</condition>
    <condition>Pro-Lymphocytic Leukemia</condition>
    <condition>Myelofibrosis</condition>
    <arm_group>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients Receive:&#xD;
  Patients receive:&#xD;
  Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2&#xD;
  Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.&#xD;
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive:&#xD;
  Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1&#xD;
  Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.&#xD;
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive:&#xD;
  Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4&#xD;
  Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.&#xD;
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive:&#xD;
  Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1&#xD;
  Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.&#xD;
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive:&#xD;
  Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1&#xD;
  Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.&#xD;
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Busulfan</intervention_name>
      <description>Given IV or PO pre-transplant as part of conditioning regimen</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>Busulfex®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>Given IV pre-transplant as part of conditioning regimen</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>Fludara®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>PBSC Hematopoietic Stem Cell Transplantation (HSCT)</intervention_name>
      <description>Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>PBSC HSCT</other_name>
      <other_name>PBSC HCT</other_name>
      <other_name>PBSC Transplantation</other_name>
      <other_name>PBSCT</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Post-Transplant Cyclophosphamide</intervention_name>
      <description>Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>Cytoxan®</other_name>
      <other_name>PTCy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mesna</intervention_name>
      <description>Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post cyclophosphamide.</description>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>Mesnex®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tacrolimus</intervention_name>
      <description>Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mycophenolate Mofetil</intervention_name>
      <description>Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>MMF</other_name>
      <other_name>Cellcept®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Patient Reported Outcomes</intervention_name>
      <description>Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.</description>
      <arm_group_label>Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>PRO</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Melphalan</intervention_name>
      <description>Given IV pre transplant as part of conditioning regimen</description>
      <arm_group_label>Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Total-body irradiation</intervention_name>
      <description>Administered pre-transplant as part of conditioning regimen</description>
      <arm_group_label>Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy</arm_group_label>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>TBI</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>Given IV pre-transplant as part of conditioning regimen</description>
      <arm_group_label>Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy</arm_group_label>
      <other_name>Cytoxan®</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Stratum 1 Recipient Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥ 18 years and &lt; 66 years (chemotherapy-based conditioning) or &lt; 61 years (total&#xD;
               body irradiation [TBI]-based conditioning) at the time of signing informed consent&#xD;
  &#xD;
            2. Patient or legally authorized representative has the ability to provide informed&#xD;
               consent according to the applicable regulatory and institutional requirements.&#xD;
  &#xD;
            3. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study.&#xD;
  &#xD;
            4. Planned MAC regimen as defined per study protocol&#xD;
  &#xD;
            5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with&#xD;
               age ≥ 18 and ≤ 40 years (≤ 35 preferred).&#xD;
  &#xD;
            6. Product planned for infusion is MMUD T-cell replete PBSC allograft&#xD;
  &#xD;
            7. HCT-CI &lt; 5. The presence of prior malignancy will not be used to calculate HCT-CI for&#xD;
               this trial to allow for the inclusion of patients with secondary or therapy-related&#xD;
               AML or MDS.&#xD;
  &#xD;
            8. One of the following diagnoses:&#xD;
  &#xD;
                 1. Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute&#xD;
                    leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating&#xD;
                    blasts or evidence of extra-medullary disease. Documentation of bone marrow&#xD;
                    assessment will be accepted within 45 days prior to the anticipated start of&#xD;
                    conditioning.&#xD;
  &#xD;
                 2. Patients with MDS with no circulating blasts and with &lt; 10% blasts in the bone&#xD;
                    marrow (higher blast percentage allowed in MDS due to lack of differences in&#xD;
                    outcomes with &lt; 5% or 5-10% blasts in MDS). Documentation of bone marrow&#xD;
                    assessment will be accepted within 45 days prior to the anticipated start of&#xD;
                    conditioning.&#xD;
  &#xD;
            9. Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent&#xD;
               echocardiogram or multi-gated acquisition scan (MUGA) results.&#xD;
  &#xD;
           10. Estimated creatinine clearance ≥ 45mL/min calculated by equation.&#xD;
  &#xD;
           11. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO)&#xD;
               corrected for hemoglobin &gt; 50% and forced expiratory volume in first second (FEV1)&#xD;
               predicted &gt; 50% based on most recent pulmonary function test (PFT) results&#xD;
  &#xD;
           12. Liver function acceptable per local institutional guidelines&#xD;
  &#xD;
           13. KPS of ≥ 70%&#xD;
  &#xD;
          Stratum 2 Recipient Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years at the time of signing informed consent&#xD;
  &#xD;
            2. Patient or legally authorized representative has the ability to provide informed&#xD;
               consent according to the applicable regulatory and local institutional requirements.&#xD;
  &#xD;
            3. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study.&#xD;
  &#xD;
            4. Planned NMA/RIC regimen per study protocol&#xD;
  &#xD;
            5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with&#xD;
               age ≥ 18 and ≤ 40 years (≤ 35 preferred).&#xD;
  &#xD;
            6. Product planned for infusion is MMUD T-cell replete PBSC allograft&#xD;
  &#xD;
            7. One of the following diagnoses:&#xD;
  &#xD;
                 1. Patients with acute leukemia or chronic myeloid leukemia (CML) with no&#xD;
                    circulating blasts, no evidence of extramedullary disease, and with &lt; 5% blasts&#xD;
                    in the bone marrow.&#xD;
  &#xD;
                    Documentation of bone marrow assessment will be accepted within 45 days prior to&#xD;
                    the anticipated start of conditioning.&#xD;
  &#xD;
                 2. Patients with MDS with no circulating blasts and with &lt; 10% blasts in the bone&#xD;
                    marrow (higher blast percentage allowed in MDS due to lack of differences in&#xD;
                    outcomes with &lt; 5% or 5-10% blasts in MDS.) Documentation of bone marrow&#xD;
                    assessment will be accepted within 45 days prior to the anticipated start of&#xD;
                    conditioning.&#xD;
  &#xD;
                 3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including&#xD;
                    prolymphocytic leukemia) with chemosensitive disease at time of transplantation&#xD;
  &#xD;
                 4. Higher risk CMML according to CMML-specific prognostic scoring system or high&#xD;
                    risk MDS/MPN not otherwise specified are eligible, provided there is no evidence&#xD;
                    of high-grade bone marrow fibrosis or massive splenomegaly at the time of&#xD;
                    enrollment.&#xD;
  &#xD;
                 5. Patients with lymphoma with chemosensitive disease at the time of transplantation&#xD;
  &#xD;
            8. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent&#xD;
               echocardiogram or MUGA results with no clinical evidence of heart failure&#xD;
  &#xD;
            9. Estimated creatinine clearance ≥ 45mL/min calculated by equation&#xD;
  &#xD;
           10. Pulmonary function: DLCO corrected for hemoglobin &gt; 50% and FEV1 predicted &gt;50% based&#xD;
               on most recent PFT results&#xD;
  &#xD;
           11. Liver function acceptable per local institutional guidelines&#xD;
  &#xD;
           12. KPS of ≥ 60%&#xD;
  &#xD;
          Stratum 3 Recipient Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years at the time of signing informed consent&#xD;
  &#xD;
            2. Patient or legally authorized representative has the ability to provide informed&#xD;
               consent according to the applicable regulatory and local institutional requirements.&#xD;
  &#xD;
            3. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study.&#xD;
  &#xD;
            4. Planned NMA/RIC regimen per study protocol&#xD;
  &#xD;
            5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with&#xD;
               age ≥ 18 and ≤ 40 years (≤ 35 preferred).&#xD;
  &#xD;
            6. Product planned for infusion is MMUD T-cell replete PBSC allograft&#xD;
  &#xD;
            7. Diagnosis of primary myelofibrosis with risk features making them eligible for HCT.&#xD;
               Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with&#xD;
               grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require&#xD;
               sponsor approval before enrolling.&#xD;
  &#xD;
            8. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent&#xD;
               echocardiogram or MUGA results with no clinical evidence of heart failure&#xD;
  &#xD;
            9. Estimated creatinine clearance ≥ 45 mL/min calculated by equation&#xD;
  &#xD;
           10. Pulmonary function: DLCO corrected for hemoglobin &gt; 50% and FEV1 predicted &gt;50% based&#xD;
               on most recent PFT results&#xD;
  &#xD;
           11. Liver function acceptable per local institutional guidelines&#xD;
  &#xD;
           12. KPS of ≥ 60%&#xD;
  &#xD;
          Donor Inclusion Criteria (note: donors are not research subjects):&#xD;
  &#xD;
            1. Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or&#xD;
               7/8 (HLA-A, -B, -C, and -DRB1.&#xD;
  &#xD;
            2. Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DQB1, and&#xD;
               -DPB1.&#xD;
  &#xD;
            3. Age ≥ 18 years and ≤ 40 years at the time of signing informed consent for PBSC&#xD;
               donation. Note: donors are preferred to be ≤ 35.&#xD;
  &#xD;
            4. Meet the donor registries' medical suitability requirements for PBSC donation.&#xD;
  &#xD;
            5. Must undergo eligibility screening according to current Food and Drug Administration&#xD;
               (FDA) requirements. Donors who do not meet one or more of the donor screening&#xD;
               requirements may donate under urgent medical need.&#xD;
  &#xD;
            6. Must agree to donate PBSC.&#xD;
  &#xD;
            7. Must have the ability to give informed consent according to standard (non-study)&#xD;
               informed consent according to applicable donor regulatory requirements.&#xD;
  &#xD;
          Recipient Exclusion Criteria (Strata 1, 2, and 3):&#xD;
  &#xD;
            1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available&#xD;
  &#xD;
            2. Subject unwilling or unable to give informed consent, or unable to comply with the&#xD;
               protocol including required follow-up and testing&#xD;
  &#xD;
            3. Subjects with a prior allogeneic transplant&#xD;
  &#xD;
            4. Subjects with an autologous transplant within the past 3 months&#xD;
  &#xD;
            5. Females who are breast-feeding or pregnant&#xD;
  &#xD;
            6. Uncontrolled bacterial, viral, or fungal infection at the time of the transplant&#xD;
               preparative regimen&#xD;
  &#xD;
            7. Concurrent enrollment on a preventative GvHD and/or infectious disease prevention&#xD;
               clinical trial.&#xD;
  &#xD;
            8. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to&#xD;
               transplant.&#xD;
  &#xD;
            9. Patients who are HIV+ with persistently positive viral load. HIV-infected patients on&#xD;
               effective anti-retroviral therapy (ART) with undetectable viral load within 6 months&#xD;
               are eligible for this trial. Patients with well controlled HIV are eligible provided&#xD;
               resistance panels are negative, the patient is compliant with ART, and their disease&#xD;
               remains well controlled.&#xD;
  &#xD;
          Donor Exclusion Criteria:&#xD;
  &#xD;
            1. Donor unwilling or unable to donate.&#xD;
  &#xD;
            2. Recipient positive for HLA antibodies against a mismatched HLA in the selected donor&#xD;
               determined by the presence of donor specific HLA antibodies (DSA) to any mismatched&#xD;
               HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4,&#xD;
               DRB5, -DQA1, - DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) &gt;3000 by&#xD;
               microarray-based single antigen bead testing. In patients receiving red blood cell or&#xD;
               platelet transfusions, DSA evaluation must be performed or repeated post-transfusion&#xD;
               and prior to donor mobilization and initiation of recipient preparative regimen.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Steven Devine, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>NMDP/Be The Match</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jeffery Auletta, MD</last_name>
      <role>Study Chair</role>
      <affiliation>NMDP/Be The Match</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Brandan Butler, MBA</last_name>
      <phone>763-406-3280</phone>
      <email>bbutler@nmdp.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lisa Erickson</last_name>
      <phone>763-406-4710</phone>
      <email>lericks2@NMDP.ORG</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Mayo Clinic - Jacksonville</name>
        <address>
          <city>Jacksonville</city>
          <state>Florida</state>
          <zip>32224</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Hemant Murthy, MD</last_name>
        <email>Murthy.Hemant@mayo.edu</email>
      </contact>
      <investigator>
        <last_name>Hemant Murthy, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Miami Sylvester Cancer Center</name>
        <address>
          <city>Miami</city>
          <state>Florida</state>
          <zip>33136</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Antonio M Jimenez Jimenez, MD</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Dana Farber Cancer Institute</name>
        <address>
          <city>Boston</city>
          <state>Massachusetts</state>
          <zip>02215</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mahasweta Gooptu, MD</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Karmanos Cancer Institute</name>
        <address>
          <city>Detroit</city>
          <state>Michigan</state>
          <zip>48201</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Dipenkumar Modi, MD</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Cancer Center - Adults</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Brian Shaffer, MD</last_name>
        <email>shaffeb1@mskcc.org</email>
      </contact>
      <investigator>
        <last_name>Brian Shaffer, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Froedtert &amp; the Medical College of Wisconsin</name>
        <address>
          <city>Milwaukee</city>
          <state>Wisconsin</state>
          <zip>53226</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Sameem Abedin, MD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lymphoma</keyword>
    <keyword>Leukemia</keyword>
    <keyword>Hematologic Diseases</keyword>
    <keyword>Myelodysplastic Syndromes</keyword>
    <keyword>Preleukemia</keyword>
    <keyword>Precursor Cell Lymphoblastic Leukemia-Lymphoma</keyword>
    <keyword>Leukemia , Lymphocytic, Chronic, B-Cell</keyword>
    <keyword>Leukemia, Myeloid, Acute</keyword>
    <keyword>Leukemia, Biphenotypic, Acute</keyword>
    <keyword>Neoplasms by Histologic Type</keyword>
    <keyword>Neoplasms</keyword>
    <keyword>Lymphoproliferative Disorders</keyword>
    <keyword>Lymphatic Diseases</keyword>
    <keyword>Immunoproliferative Disorders</keyword>
    <keyword>Immune System Disorders</keyword>
    <keyword>Bone Marrow Diseases</keyword>
    <keyword>Precancerous Conditions</keyword>
    <keyword>Leukemia, Lymphoid</keyword>
    <keyword>Leukemia, B-Cell</keyword>
    <keyword>Leukemia, Myeloid</keyword>
    <keyword>Cyclophosphamide</keyword>
    <keyword>Mesna</keyword>
    <keyword>Tacrolimus</keyword>
    <keyword>Busulfan</keyword>
    <keyword>Fludarabine</keyword>
    <keyword>Total Body Irradiation</keyword>
    <keyword>Melphalan</keyword>
    <keyword>Mycophenolate mofetil</keyword>
    <keyword>Reduced Dose Cyclophosphamide</keyword>
    <keyword>Immunosuppressive Agents</keyword>
    <keyword>Immunologic Factors</keyword>
    <keyword>Physiological Effects of Drugs</keyword>
    <keyword>Hematopoietic Stem Cell Transplantation</keyword>
    <keyword>Peripheral Blood Stem Cells</keyword>
    <keyword>Unrelated Donors</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>Neoplasms</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Preleukemia</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
      <mesh_term>Leukemia, Lymphoid</mesh_term>
      <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
      <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
      <mesh_term>Leukemia, Myelomonocytic, Chronic</mesh_term>
      <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
      <mesh_term>Leukemia, Prolymphocytic</mesh_term>
      <mesh_term>Myelodysplastic Syndromes</mesh_term>
      <mesh_term>Myeloproliferative Disorders</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>Cyclophosphamide</mesh_term>
      <mesh_term>Melphalan</mesh_term>
      <mesh_term>Busulfan</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Tacrolimus</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06001385
  org study id: OPTIMIZE
  nct id: NCT06001385
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to determine the effectiveness of Reduced Dose
        Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after
        receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question[s] it aims to answer
        are:
  
          -  Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days
             after transplant?
  
          -  Does a reduced dose of PTCy maintain the same level of protection against Graft Versus
             Host Disease (GvHD) as the standard dose of PTCy?
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Infection Free Survival
  time frame: 100 days post-HCT
  description: Survival at 100 days without grades 2-3 infections (per BMT CTN grading criteria)
  measure: Overall Survival
  time frame: 1-year post-HCT
  description: Defined as time interval between date of transplant and death from any cause
  measure: Progression-free survival
  time frame: 1-year post-HCT
  description: Defined as disease relapse or progression, or death by any cause
  measure: Infection-free survival
  time frame: 1-year post-HCT
  description: Defined as death and grades II-III infection (per BMT CTN criteria)
  measure: Graft versus host disease relapse free survival
  time frame: 1-year post-HCT
  description: Defined as relapse or progression of underling disease (by 1 year), grade III-IV acute GvHD (by 6 months), chronic GvHD requiring systemic immune suppression (by 1 year), or death by any cause (by 1 year).
  measure: Non-relapse mortality
  time frame: 1-year post-HCT
  description: Defined as death without evidence of disease progression or recurrence
  measure: Cumulative incidence of neutrophil recovery
  time frame: Day 28 post-HCT
  description: Defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days
  measure: Cumulative incidence of platelet recovery
  time frame: Day 28 post-HCT
  description: Defined as platelet count ≥20,000/mm^3 or ≥50,000/mm^3 with no platelet transfusions within seven days.
  measure: Cumulative incidence of primary and secondary graft failure
  time frame: Day 28 and 1-year post-HCT
  description: Primary graft failure is defined as no neutrophil recovery to ≥ 500 cells/mm3 by Day 28 post HCT.
  Secondary graft failure is defined as as initial neutrophil count recovery followed by subsequent decline in absolute neutrophil counts <500 cells/mm3, unresponsive to growth factor therapy, but cannot be explained by infection, disease relapse, or medications.
  measure: Donor T-Cell Chimerism
  time frame: Day 28, 100 and 365 post-HCT
  description: Defined as percent of donor chimerism via peripheral blood
  measure: Cumulative incidence of acute GvHD
  time frame: Day 100 and Day 180 post-HCT
  description: Defined as cumulative incidence of grades II-IV acute GvHD
  measure: Cumulative incidence of chronic GvHD
  time frame: 1-year post-HCT
  measure: Cumulative incidence of grade 2-3 bacterial, fungal, and viral infections
  time frame: Day 100 and 1-year post-HCT
  description: Defined as grades 2-3 infection as defined by BMT CTN grading criteria.
  measure: Cumulative incidence of grades 2-3 BK virus hemorrhagic cystitis
  time frame: 1-year post-HCT
  description: Defined as incidence of BK virus hemorrhagic cystitis per BMT CTN grading criteria
  measure: Cumulative incidence of relapse/progression
  time frame: 1-year post-HCT
  description: Defined as disease relapse or progression from Day 0 to 1-year post-HCT
  measure: Overall Toxicity
  time frame: 1-year post-HCT
  description: To tabulate adverse events (AEs, experienced by recipients, defined as grade 3-5 unexpected and grade 5 expected AEs according to CTCAE v5
  measure: Incidence and Severity of cytokine release syndrome
  time frame: within 14 days post-HCT
  description: Defined and graded using the ASTCT grading criteria.
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group type: Experimental
  description: Patients Receive:
  Patients receive:
  Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
  Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group type: Experimental
  description: Patients receive:
  Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
  Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group type: Experimental
  description: Patients receive:
  Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
  Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group type: Experimental
  description: Patients receive:
  Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
  Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  arm group type: Experimental
  description: Patients receive:
  Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
  Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
  Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
  intervention type: Drug
  intervention name: Busulfan
  description: Given IV or PO pre-transplant as part of conditioning regimen
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  other name: Busulfex®
  intervention type: Drug
  intervention name: Fludarabine
  description: Given IV pre-transplant as part of conditioning regimen
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: Fludara®
  intervention type: Procedure
  intervention name: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
  description: Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: PBSC HSCT
  other name: PBSC HCT
  other name: PBSC Transplantation
  other name: PBSCT
  intervention type: Drug
  intervention name: Post-Transplant Cyclophosphamide
  description: Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: Cytoxan®
  other name: PTCy
  intervention type: Drug
  intervention name: Mesna
  description: Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post cyclophosphamide.
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: Mesnex®
  intervention type: Drug
  intervention name: Tacrolimus
  description: Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  intervention type: Drug
  intervention name: Mycophenolate Mofetil
  description: Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: MMF
  other name: Cellcept®
  intervention type: Other
  intervention name: Patient Reported Outcomes
  description: Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
  arm group label: Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: PRO
  intervention type: Drug
  intervention name: Melphalan
  description: Given IV pre transplant as part of conditioning regimen
  arm group label: Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
  intervention type: Radiation
  intervention name: Total-body irradiation
  description: Administered pre-transplant as part of conditioning regimen
  arm group label: Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: TBI
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: Given IV pre-transplant as part of conditioning regimen
  arm group label: Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
  other name: Cytoxan®
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Steven Devine, MD
  role: Principal Investigator
  affiliation: NMDP/Be The Match
  last name: Jeffery Auletta, MD
  role: Study Chair
  affiliation: NMDP/Be The Match
  last name: Brandan Butler, MBA
  phone: 763-406-3280
  email: bbutler@nmdp.org
  last name: Lisa Erickson
  phone: 763-406-4710
  email: lericks2@NMDP.ORG
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Leukemia
  mesh term: Neoplasms
  mesh term: Leukemia, Myeloid
  mesh term: Preleukemia
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Leukemia, Lymphoid
  mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
  mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  mesh term: Leukemia, Myelomonocytic, Chronic
  mesh term: Leukemia, Myelomonocytic, Juvenile
  mesh term: Leukemia, Prolymphocytic
  mesh term: Myelodysplastic Syndromes
  mesh term: Myeloproliferative Disorders
  mesh term: Mycophenolic Acid
  mesh term: Cyclophosphamide
  mesh term: Melphalan
  mesh term: Busulfan
  mesh term: Fludarabine
  mesh term: Tacrolimus
  sharing ipd: No