<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/NCT02220985</url>
  </required_header>
  <id_info>
    <org_study_id>2684.00</org_study_id>
    <secondary_id>NCI-2014-01301</secondary_id>
    <secondary_id>2684.00</secondary_id>
    <secondary_id>R01HL121568</secondary_id>
    <secondary_id>RG9214012</secondary_id>
    <secondary_id>2P01CA018029</secondary_id>
    <nct_id>NCT02220985</nct_id>
  </id_info>
  <brief_title>Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD</brief_title>
  <official_title>A Phase II Study Evaluating Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors for Prevention of GVHD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Fred Hutchinson Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia,&#xD;
      myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral&#xD;
      blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and&#xD;
      total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the&#xD;
      patient's normal blood cells, especially immune cells that could reject the donor cells.&#xD;
      Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem&#xD;
      cells will grow and eventually replace the patient's original blood system, including red&#xD;
      cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels,&#xD;
      and multiple types of immune-system white blood cells that fight infections. Mature donor&#xD;
      immune cells, especially a type of immune cell called T lymphocytes (or T cells) are&#xD;
      transferred along with these blood-forming stem cells. T cells are a major part of the&#xD;
      curative power of transplantation because they can attack leukemia cells that have survived&#xD;
      the chemo/radiation therapy and also help to fight infections after transplantation. However,&#xD;
      donor T cells can also attack a patient's healthy tissues in an often-dangerous condition&#xD;
      known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to&#xD;
      decrease the severity of GVHD; however, they are incompletely effective and prolonged&#xD;
      immunosuppression used to prevent and treat GVHD significantly increases the risk of serious&#xD;
      infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing&#xD;
      so also profoundly delays infection-fighting immune reconstitution and eliminates the&#xD;
      possibility that donor immune cells will kill residual leukemia cells. Work in animal models&#xD;
      found that depleting a type of T cell, called naïve T cells or T cells that have never&#xD;
      responded to an infection, can diminish GVHD while at least in part preserving some of the&#xD;
      benefits of donor T cells including resistance to infection and the ability to kill leukemia&#xD;
      cells. This clinical trial studies how well the selective removal of naïve T cells works in&#xD;
      preventing GVHD after peripheral blood stem cell transplants. This study will include&#xD;
      patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor&#xD;
      grafts from related or unrelated donors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE: Patients are assigned to 1 of 4 treatment arms.&#xD;
&#xD;
      CONDITIONING:&#xD;
&#xD;
      ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body&#xD;
      irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously&#xD;
      (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6&#xD;
      to -2.&#xD;
&#xD;
      ARMS B AND D (lower-intensity myeloablative conditioning): Patients receive cyclophosphamide&#xD;
      IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and&#xD;
      thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation once&#xD;
      daily (QD) on days -2 and -1.&#xD;
&#xD;
      TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating&#xD;
      factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.&#xD;
&#xD;
      GVHD PROPHYLAXIS:&#xD;
&#xD;
      ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally&#xD;
      (PO) (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive&#xD;
      methotrexate IV on days 1, 3, 6, and 11.&#xD;
&#xD;
      ARMS B AND D: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if&#xD;
      given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on days -3 to&#xD;
      approximately day 30, with or without taper at the discretion of the treating physician.&#xD;
      Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low,&#xD;
      after discussion with the principal investigator.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 80-100 days, 360 days, and&#xD;
      then yearly for up to 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 3, 2015</start_date>
  <completion_date type="Anticipated">April 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2025</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>Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Match related donor (MRD)-high intensity (Arm A), MRD-lower intensity (Arm B), match unrelated donor (MUD)-high intensity (Arm C) and MUD-lower intensity (Arm D) cohorts will be analyzed separately.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to completion of prednisone</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to completion of all immunosuppression</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Requirement of immunosuppression after transplant</measure>
    <time_frame>At 2 years after transplant</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of acute graft-versus-host disease (GVHD) grades II-IV</measure>
    <time_frame>Up to day 100</time_frame>
    <description>Defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management</measure>
    <time_frame>Up to day 100</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Graft failure</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Defined operationally as failure to reach an absolute neutrophil count (ANC) of &gt; 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to &lt; 100 after an established donor graft.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to absolute neutrophil count (ANC) of &gt; 500/uL on the first of three consecutive days</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to absolute neutrophil count (ANC) of &gt; 1,000/uL on the first of three consecutive test results</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to platelet count &gt; 20,000/uL for 3 days without transfusion</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to platelet count &gt; 50,000/uL for 3 days without transfusion</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chimerism analysis</measure>
    <time_frame>Up to 360 days</time_frame>
    <description>Will be analyzed from peripheral blood or marrow.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transplant related mortality</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Defined as mortality in any patient for whom there has not been a diagnosis of relapse.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Acute Biphenotypic Leukemia</condition>
  <condition>Acute Leukemia of Ambiguous Lineage</condition>
  <condition>Acute Undifferentiated Leukemia</condition>
  <condition>Allogeneic Hematopoietic Stem Cell Transplant Recipient</condition>
  <condition>Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Blastic Plasmacytoid Dendritic Cell Neoplasm</condition>
  <condition>Childhood Acute Lymphoblastic Leukemia in Remission</condition>
  <condition>Childhood Acute Myeloid Leukemia in Remission</condition>
  <condition>Donor</condition>
  <condition>Lymphoblastic Lymphoma</condition>
  <condition>Myelodysplastic Syndrome With Excess Blasts</condition>
  <condition>Myelodysplastic Syndrome With Excess Blasts-1</condition>
  <condition>Myelodysplastic Syndrome With Excess Blasts-2</condition>
  <condition>Recurrent Acute Lymphoblastic Leukemia</condition>
  <condition>Recurrent Acute Myeloid Leukemia</condition>
  <condition>Recurrent Childhood Acute Lymphoblastic Leukemia</condition>
  <condition>Recurrent Childhood Acute Myeloid Leukemia</condition>
  <condition>Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Refractory Acute Lymphoblastic Leukemia</condition>
  <condition>Refractory Acute Myeloid Leukemia</condition>
  <condition>Acute Lymphoblastic Leukemia in Remission</condition>
  <condition>Acute Myeloid Leukemia in Remission</condition>
  <arm_group>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.&#xD;
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.&#xD;
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1.&#xD;
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.&#xD;
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.&#xD;
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.&#xD;
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1.&#xD;
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.&#xD;
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic HSCT</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>Allogeneic Hematopoietic Cell Transplantation</other_name>
    <other_name>Allogeneic Stem Cell Transplantation</other_name>
    <other_name>HSC</other_name>
    <other_name>HSCT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>2-F-ara-AMP</other_name>
    <other_name>9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-</other_name>
    <other_name>Beneflur</other_name>
    <other_name>Fludara</other_name>
    <other_name>SH T 586</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <other_name>Abitrexate</other_name>
    <other_name>Alpha-Methopterin</other_name>
    <other_name>Amethopterin</other_name>
    <other_name>Brimexate</other_name>
    <other_name>CL 14377</other_name>
    <other_name>CL-14377</other_name>
    <other_name>Emtexate</other_name>
    <other_name>Emthexat</other_name>
    <other_name>Emthexate</other_name>
    <other_name>Farmitrexat</other_name>
    <other_name>Fauldexato</other_name>
    <other_name>Folex</other_name>
    <other_name>Folex PFS</other_name>
    <other_name>Lantarel</other_name>
    <other_name>Ledertrexate</other_name>
    <other_name>Lumexon</other_name>
    <other_name>Maxtrex</other_name>
    <other_name>Medsatrexate</other_name>
    <other_name>Metex</other_name>
    <other_name>Methoblastin</other_name>
    <other_name>Methotrexate LPF</other_name>
    <other_name>Methotrexate Methylaminopterin</other_name>
    <other_name>Methotrexatum</other_name>
    <other_name>Metotrexato</other_name>
    <other_name>Metrotex</other_name>
    <other_name>Mexate</other_name>
    <other_name>Mexate-AQ</other_name>
    <other_name>MTX</other_name>
    <other_name>Novatrex</other_name>
    <other_name>Rheumatrex</other_name>
    <other_name>Texate</other_name>
    <other_name>Tremetex</other_name>
    <other_name>Trexeron</other_name>
    <other_name>Trixilem</other_name>
    <other_name>WR-19039</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Given IV and PO</description>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>Cellcept</other_name>
    <other_name>MMF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>PBPC transplantation</other_name>
    <other_name>PBSCT</other_name>
    <other_name>Peripheral Blood Progenitor Cell Transplantation</other_name>
    <other_name>Peripheral Stem Cell Support</other_name>
    <other_name>Peripheral Stem Cell Transplant</other_name>
    <other_name>Peripheral Stem Cell Transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo PBSCT with CD45RA-depleted cells</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>PBPC transplantation</other_name>
    <other_name>PBSCT</other_name>
    <other_name>Peripheral Blood Progenitor Cell Transplantation</other_name>
    <other_name>Peripheral Stem Cell Support</other_name>
    <other_name>Peripheral Stem Cell Transplant</other_name>
    <other_name>Peripheral Stem Cell Transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>FK 506</other_name>
    <other_name>Fujimycin</other_name>
    <other_name>Hecoria</other_name>
    <other_name>Prograf</other_name>
    <other_name>Protopic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiotepa</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <arm_group_label>Arm D (MUD)</arm_group_label>
    <other_name>1,1',1''-Phosphinothioylidynetrisaziridine</other_name>
    <other_name>Girostan</other_name>
    <other_name>N,N', N''-Triethylenethiophosphoramide</other_name>
    <other_name>Oncotiotepa</other_name>
    <other_name>STEPA</other_name>
    <other_name>Tepadina</other_name>
    <other_name>TESPA</other_name>
    <other_name>Tespamin</other_name>
    <other_name>Tespamine</other_name>
    <other_name>Thio-Tepa</other_name>
    <other_name>Thiofosfamide</other_name>
    <other_name>Thiofozil</other_name>
    <other_name>Thiophosphamide</other_name>
    <other_name>Thiophosphoramide</other_name>
    <other_name>Thiotef</other_name>
    <other_name>Tifosyl</other_name>
    <other_name>TIO TEF</other_name>
    <other_name>Tio-tef</other_name>
    <other_name>Triethylene thiophosphoramide</other_name>
    <other_name>Triethylenethiophosphoramide</other_name>
    <other_name>Tris(1-aziridinyl)phosphine sulfide</other_name>
    <other_name>TSPA</other_name>
    <other_name>WR 45312</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total-Body Irradiation</intervention_name>
    <description>Undergo TBI</description>
    <arm_group_label>Arm A (MRD)</arm_group_label>
    <arm_group_label>Arm B (MRD)</arm_group_label>
    <arm_group_label>Arm C (MUD)</arm_group_label>
    <other_name>Total Body Irradiation</other_name>
    <other_name>Whole-Body Irradiation</other_name>
    <other_name>TBI</other_name>
    <other_name>Whole Body Irradiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are considered appropriate candidates for allogeneic hematopoietic stem&#xD;
             cell transplantation and have one of the following diagnoses:&#xD;
&#xD;
               -  Acute lymphocytic leukemia in first or subsequent remission&#xD;
&#xD;
               -  Acute myeloid leukemia in first or subsequent remission&#xD;
&#xD;
               -  Acute lymphocytic leukemia in relapse or primary refractory disease with a&#xD;
                  circulating blast count of no more than 10,000/mm^3 (Arms A or C only)&#xD;
&#xD;
               -  Acute myeloid leukemia in relapse or primary refractory disease with a&#xD;
                  circulating blast count of no more than 10,000/mm^3 (Arms A or C only)&#xD;
&#xD;
               -  Refractory anemia with excess blasts (RAEB-1 and RAEB-2) (if the patient has&#xD;
                  received previous induction chemotherapy within 60 days)&#xD;
&#xD;
               -  Chronic myelogenous leukemia with a history of accelerated phase or blast crisis&#xD;
                  (if the patient has received at least one course of induction chemotherapy)&#xD;
&#xD;
               -  Other acute leukemia or related neoplasm (including but not limited to&#xD;
                  'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia, blastic&#xD;
                  plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma)&#xD;
&#xD;
          -  Patients 0-49 years old will be enrolled in Arm A or C (high-intensity)&#xD;
&#xD;
          -  Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients&#xD;
             eligible for Arms B or D also include those who have received previous allogeneic HCT,&#xD;
             or who have co-morbid conditions rendering them unsuitable for high-dose conditioning,&#xD;
             determined in consultation with the principal investigator&#xD;
&#xD;
          -  Patient with a HLA-matched (HLA-A, B, C, and DR beta 1 [DRB1] molecularly matched)&#xD;
             unrelated donor or related donor capable of donating PBSC&#xD;
&#xD;
          -  DONOR INCLUSION:&#xD;
&#xD;
          -  HLA-matched related donors &gt;= 18 years and capable and willing to donate PBSC (Arms A&#xD;
             and B)&#xD;
&#xD;
          -  HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution&#xD;
             typing) capable and willing to donate PBSC (Arms C and D)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with central nervous system (CNS) involvement refractory to intrathecal&#xD;
             chemotherapy and/or standard cranial-spinal radiation&#xD;
&#xD;
          -  Patients on other experimental protocols for prevention of acute GVHD&#xD;
&#xD;
          -  Patient weight &gt;= 100 kg; patients &gt;= 70 kg with MUDs must be discussed with the&#xD;
             principal investigator&#xD;
&#xD;
          -  Patients who are human immunodeficiency virus positive (HIV+)&#xD;
&#xD;
          -  Patients with uncontrolled infections for whom myeloablative HCT is considered&#xD;
             contraindicated by the consulting infectious disease physician (upper respiratory&#xD;
             tract viral infection does not constitute an uncontrolled infection in this context)&#xD;
&#xD;
          -  Patients with organ dysfunction&#xD;
&#xD;
          -  ARM A OR C EXCLUSION:&#xD;
&#xD;
          -  Creatinine &gt; 1.5 mg/dl at the present time; patients with a known history of&#xD;
             creatinine &gt; 1.5 mg/dl must have a current estimated creatinine clearance of &gt; 40&#xD;
             ml/min&#xD;
&#xD;
          -  Cardiac ejection fraction &lt; 45%&#xD;
&#xD;
          -  Diffusing capacity of the lung for carbon monoxide (DLCO) corrected &lt; 60%; patients&#xD;
             who are unable to perform pulmonary function tests (for example, due to young age&#xD;
             and/or developmental status) will be excluded if the oxygen (O2) saturation is &lt; 92%&#xD;
             on room air&#xD;
&#xD;
          -  Liver function abnormality; patients who have liver function tests (LFTs) (including&#xD;
             total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT])&#xD;
             &gt;= twice the upper limit of normal should be evaluated by a gastrointestinal (GI)&#xD;
             physician; unless there is a clear precipitating factor (such as an azole,&#xD;
             methotrexate, Bactrim or another drug); if the GI physician considers that HCT on the&#xD;
             high-intensity arms of protocol is contraindicated for that patient the patient may be&#xD;
             considered for treatment on the lower intensity arm of the protocol or excluded from&#xD;
             the protocol; patients with Gilbert's syndrome and no other known liver function&#xD;
             abnormality and patients with reversible drug-related transaminitis do not necessarily&#xD;
             require GI consultation and may be included on the high-intensity arms of the protocol&#xD;
&#xD;
          -  ARM B OR D EXCLUSION:&#xD;
&#xD;
          -  Creatinine &gt; 2.0 mg/dl at the present time; patients with a known history of&#xD;
             creatinine &gt; 1.5 mg/dl must have a current estimated creatinine clearance &gt; 40 ml/min&#xD;
&#xD;
          -  Cardiac ejection fraction &lt; 35%&#xD;
&#xD;
          -  DLCO corrected &lt; 50%; patients who are unable to perform pulmonary function tests (for&#xD;
             example, due to young age and/or developmental status) will be excluded if the O2&#xD;
             saturation is &lt; 92% on room air; patients with a DLCO 50-60% must also have a partial&#xD;
             pressure of oxygen (pO2) of &gt; 80 mmHg&#xD;
&#xD;
          -  Liver function abnormality; patients who have LFTs &gt;= twice the upper limit of normal&#xD;
             should be evaluated by a GI physician unless there is a clear precipitating factor&#xD;
             (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant&#xD;
             liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis,&#xD;
             alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices,&#xD;
             hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by&#xD;
             prolongation of the prothrombin time, ascites related to portal hypertension,&#xD;
             bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total&#xD;
             serum bilirubin &gt; 3 mg/dL, and symptomatic biliary disease will be excluded&#xD;
&#xD;
          -  Patients will be excluded from Arms A and C if they have received a previous&#xD;
             myeloablative transplant; patients who have received a prior HCT at least 6 months&#xD;
             prior may be considered for inclusion on Arms B or D after discussion with the&#xD;
             principal investigator (PI)&#xD;
&#xD;
          -  Patients with a life expectancy &lt; 3 months from co-existing disease other than the&#xD;
             leukemia or RAEB&#xD;
&#xD;
          -  Patients who are pregnant or breast-feeding&#xD;
&#xD;
          -  Fertile patients of child bearing age unwilling to use contraception during and for 12&#xD;
             months post-transplant&#xD;
&#xD;
          -  Patients with a significant other medical conditions that would make them unsuitable&#xD;
             for transplant&#xD;
&#xD;
          -  Patients with a known hypersensitivity to tacrolimus, methotrexate (Arm A or C) or MMF&#xD;
             (Arm B or D)&#xD;
&#xD;
          -  DONOR EXCLUSION:&#xD;
&#xD;
          -  Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive&#xD;
             or with active hepatitis B or hepatitis C virus infection&#xD;
&#xD;
          -  Donors who fail eligibility requirements for donation of cells or tissue for donation&#xD;
             of a Human Cell and Tissue Products (HCT/P) will be excluded unless use of the cells&#xD;
             complies urgent medical need or allogeneic use in a first-degree or second-degree&#xD;
             relative&#xD;
&#xD;
          -  Unrelated donors donating outside of the United States of America (USA)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie Bleakley</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Leukemia, Myeloid, Accelerated Phase</mesh_term>
    <mesh_term>Blast Crisis</mesh_term>
    <mesh_term>Leukemia, Biphenotypic, Acute</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Anemia, Refractory, with Excess of Blasts</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Recurrence</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>Thiotepa</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02220985
org study id: 2684.00
secondary id: NCI-2014-01301
secondary id: 2684.00
secondary id: R01HL121568
secondary id: RG9214012
secondary id: 2P01CA018029
nct id: NCT02220985
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia,
      myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral
      blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and
      total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the
      patient's normal blood cells, especially immune cells that could reject the donor cells.
      Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem
      cells will grow and eventually replace the patient's original blood system, including red
      cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels,
      and multiple types of immune-system white blood cells that fight infections. Mature donor
      immune cells, especially a type of immune cell called T lymphocytes (or T cells) are
      transferred along with these blood-forming stem cells. T cells are a major part of the
      curative power of transplantation because they can attack leukemia cells that have survived
      the chemo/radiation therapy and also help to fight infections after transplantation. However,
      donor T cells can also attack a patient's healthy tissues in an often-dangerous condition
      known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to
      decrease the severity of GVHD; however, they are incompletely effective and prolonged
      immunosuppression used to prevent and treat GVHD significantly increases the risk of serious
      infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing
      so also profoundly delays infection-fighting immune reconstitution and eliminates the
      possibility that donor immune cells will kill residual leukemia cells. Work in animal models
      found that depleting a type of T cell, called naïve T cells or T cells that have never
      responded to an infection, can diminish GVHD while at least in part preserving some of the
      benefits of donor T cells including resistance to infection and the ability to kill leukemia
      cells. This clinical trial studies how well the selective removal of naïve T cells works in
      preventing GVHD after peripheral blood stem cell transplants. This study will include
      patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor
      grafts from related or unrelated donors.
OUTLINE: Patients are assigned to 1 of 4 treatment arms.

      CONDITIONING:

      ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body
      irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously
      (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6
      to -2.

      ARMS B AND D (lower-intensity myeloablative conditioning): Patients receive cyclophosphamide
      IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and
      thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation once
      daily (QD) on days -2 and -1.

      TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating
      factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.

      GVHD PROPHYLAXIS:

      ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally
      (PO) (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive
      methotrexate IV on days 1, 3, 6, and 11.

      ARMS B AND D: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if
      given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on days -3 to
      approximately day 30, with or without taper at the discretion of the treating physician.
      Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low,
      after discussion with the principal investigator.

      After completion of study treatment, patients are followed up at 80-100 days, 360 days, and
      then yearly for up to 5 years.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression
time frame: Up to 5 years
description: Match related donor (MRD)-high intensity (Arm A), MRD-lower intensity (Arm B), match unrelated donor (MUD)-high intensity (Arm C) and MUD-lower intensity (Arm D) cohorts will be analyzed separately.
measure: Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine)
time frame: Up to 5 years
measure: Time to completion of prednisone
time frame: Up to 5 years
measure: Time to completion of all immunosuppression
time frame: Up to 5 years
measure: Requirement of immunosuppression after transplant
time frame: At 2 years after transplant
measure: Presence of acute graft-versus-host disease (GVHD) grades II-IV
time frame: Up to day 100
description: Defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver.
measure: Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management
time frame: Up to day 100
measure: Graft failure
time frame: Up to day 28
description: Defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft.
measure: Time to absolute neutrophil count (ANC) of > 500/uL on the first of three consecutive days
time frame: Up to 5 years
measure: Time to absolute neutrophil count (ANC) of > 1,000/uL on the first of three consecutive test results
time frame: Up to 5 years
measure: Time to platelet count > 20,000/uL for 3 days without transfusion
time frame: Up to 5 years
measure: Time to platelet count > 50,000/uL for 3 days without transfusion
time frame: Up to 5 years
measure: Chimerism analysis
time frame: Up to 360 days
description: Will be analyzed from peripheral blood or marrow.
measure: Relapse
time frame: Up to 5 years
description: Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology.
measure: Transplant related mortality
time frame: Up to 5 years
description: Defined as mortality in any patient for whom there has not been a diagnosis of relapse.
arm group label: Arm A (MRD)
arm group type: Experimental
description: HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
arm group label: Arm B (MRD)
arm group type: Experimental
description: LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1.
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.
arm group label: Arm C (MUD)
arm group type: Experimental
description: HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
arm group label: Arm D (MUD)
arm group type: Experimental
description: LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1.
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.
GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo allogeneic HSCT
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: Allogeneic Hematopoietic Cell Transplantation
other name: Allogeneic Stem Cell Transplantation
other name: HSC
other name: HSCT
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: 2-F-ara-AMP
other name: 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
other name: Beneflur
other name: Fludara
other name: SH T 586
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
intervention type: Drug
intervention name: Methotrexate
description: Given IV
arm group label: Arm A (MRD)
arm group label: Arm C (MUD)
other name: Abitrexate
other name: Alpha-Methopterin
other name: Amethopterin
other name: Brimexate
other name: CL 14377
other name: CL-14377
other name: Emtexate
other name: Emthexat
other name: Emthexate
other name: Farmitrexat
other name: Fauldexato
other name: Folex
other name: Folex PFS
other name: Lantarel
other name: Ledertrexate
other name: Lumexon
other name: Maxtrex
other name: Medsatrexate
other name: Metex
other name: Methoblastin
other name: Methotrexate LPF
other name: Methotrexate Methylaminopterin
other name: Methotrexatum
other name: Metotrexato
other name: Metrotex
other name: Mexate
other name: Mexate-AQ
other name: MTX
other name: Novatrex
other name: Rheumatrex
other name: Texate
other name: Tremetex
other name: Trexeron
other name: Trixilem
other name: WR-19039
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Given IV and PO
arm group label: Arm B (MRD)
arm group label: Arm D (MUD)
other name: Cellcept
other name: MMF
intervention type: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: PBPC transplantation
other name: PBSCT
other name: Peripheral Blood Progenitor Cell Transplantation
other name: Peripheral Stem Cell Support
other name: Peripheral Stem Cell Transplant
other name: Peripheral Stem Cell Transplantation
intervention type: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo PBSCT with CD45RA-depleted cells
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: PBPC transplantation
other name: PBSCT
other name: Peripheral Blood Progenitor Cell Transplantation
other name: Peripheral Stem Cell Support
other name: Peripheral Stem Cell Transplant
other name: Peripheral Stem Cell Transplantation
intervention type: Drug
intervention name: Tacrolimus
description: Given IV or PO
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: FK 506
other name: Fujimycin
other name: Hecoria
other name: Prograf
other name: Protopic
intervention type: Drug
intervention name: Thiotepa
description: Given IV
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
arm group label: Arm D (MUD)
other name: 1,1',1''-Phosphinothioylidynetrisaziridine
other name: Girostan
other name: N,N', N''-Triethylenethiophosphoramide
other name: Oncotiotepa
other name: STEPA
other name: Tepadina
other name: TESPA
other name: Tespamin
other name: Tespamine
other name: Thio-Tepa
other name: Thiofosfamide
other name: Thiofozil
other name: Thiophosphamide
other name: Thiophosphoramide
other name: Thiotef
other name: Tifosyl
other name: TIO TEF
other name: Tio-tef
other name: Triethylene thiophosphoramide
other name: Triethylenethiophosphoramide
other name: Tris(1-aziridinyl)phosphine sulfide
other name: TSPA
other name: WR 45312
intervention type: Radiation
intervention name: Total-Body Irradiation
description: Undergo TBI
arm group label: Arm A (MRD)
arm group label: Arm B (MRD)
arm group label: Arm C (MUD)
other name: Total Body Irradiation
other name: Whole-Body Irradiation
other name: TBI
other name: Whole Body Irradiation
criteria: 
gender: All
minimum age: N/A
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marie Bleakley
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Leukemia, Myeloid, Accelerated Phase
mesh term: Blast Crisis
mesh term: Leukemia, Biphenotypic, Acute
mesh term: Myelodysplastic Syndromes
mesh term: Anemia, Refractory, with Excess of Blasts
mesh term: Syndrome
mesh term: Recurrence
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Thiotepa
mesh term: Methotrexate
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Tacrolimus