<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/NCT03246906</url>
  </required_header>
  <id_info>
    <org_study_id>9816</org_study_id>
    <secondary_id>NCI-2017-01311</secondary_id>
    <secondary_id>9816</secondary_id>
    <secondary_id>P01CA078902</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG9217021</secondary_id>
    <nct_id>NCT03246906</nct_id>
  </id_info>
  <brief_title>Comparison of Triple GVHD Prophylaxis Regimens for Nonmyeloablative or Reduced Intensity Conditioning Unrelated Mobilized Blood Cell Transplantation</brief_title>
  <official_title>A Randomized Phase II Study to Compare the Net Clinical Benefit of Cyclosporine and Sirolimus Combined With MMF or Post-Transplant Cyclophosphamide as GVHD Prophylaxis After HLA-Matched or HLA-Mismatched Unrelated G-CSF Mobilized Blood Cell Transplantation Using Nonmyeloablative or Reduced Intensity Conditioning for Patients With Hematologic Malignancies</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 Institutes of Health (NIH)</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 randomized phase II trial includes a blood stem cell transplant from an unrelated donor&#xD;
      to treat blood cancer. The treatment also includes chemotherapy drugs, but in lower doses&#xD;
      than conventional (standard) stem cell transplants. The researchers will compare two&#xD;
      different drug combinations used to reduce the risk of a common but serious complication&#xD;
      called &quot;graft versus host disease&quot; (GVHD) following the transplant. Two drugs, cyclosporine&#xD;
      (CSP) and sirolimus (SIR), will be combined with either mycophenolate mofetil (MMF) or&#xD;
      post-transplant cyclophosphamide (PTCy). This part of the transplant procedure is the main&#xD;
      research focus of the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients undergo allogeneic hematopoietic stem cell transplant (HCT) at day 0.&#xD;
      Patients with an HLA-matched unrelated donor receive mycophenolate mofetil orally (PO) on&#xD;
      days 0 to 40, cyclosporine PO every 12 hours twice daily (BID) on days -3 to 96 then tapered&#xD;
      to day 150, and sirolimus PO once daily (QD) on days -3 to day 150 then tapered to day 180.&#xD;
      Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then&#xD;
      tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and&#xD;
      sirolimus PO QD on days -3 to 180 then tapered to day 365.&#xD;
&#xD;
      ARM II: Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive&#xD;
      cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then&#xD;
      tapered to day 180, and cyclophosphamide intravenously (IV) on days 3 and 4. Patients with an&#xD;
      HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180,&#xD;
      sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and&#xD;
      4.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 6 months and every year&#xD;
      thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Anticipated">October 11, 2026</completion_date>
  <primary_completion_date type="Anticipated">October 11, 2026</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Chronic graft versus host disease (GVHD)-free, relapse-free survival (CRFS)</measure>
    <time_frame>At 1 year post- hematopoietic cell transplantation (HCT)</time_frame>
    <description>Composite time-to-event outcome in which events include moderate or severe chronic GVHD based on National Institute of Health consensus criteria, relapse, or death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Grades II-IV and III-IV acute graft versus host disease (GVHD)</measure>
    <time_frame>At day 100 post-HCT</time_frame>
    <description>Estimated by cumulative incidence methods. Grading is based on &quot;Graft-vs-host disease&quot; Sullivan, Keith M. Hematopoietic Cell Transplantation Ed: D. Thomas, K. Blume, S. Forman, Blackwell Sciences; 1999, pages 518-519.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late graft versus host disease (GVHD) not meeting National Institute of Health (NIH) consensus criteria for chronic GVHD</measure>
    <time_frame>At 1 year post-HCT</time_frame>
    <description>GVHD occurring after day 100 and not meeting NIH consensus criteria for chronic GVHD. Estimated by cumulative incidence methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Moderate and severe chronic graft versus host disease</measure>
    <time_frame>At 1 year post-HCT</time_frame>
    <description>Estimated by cumulative incidence methods. Based on NIH consensus criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse</measure>
    <time_frame>At 1 year post-HCT</time_frame>
    <description>Estimated by cumulative incidence methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality</measure>
    <time_frame>At 1 year post-HCT</time_frame>
    <description>Estimated by cumulative incidence methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression or relapse-free survival</measure>
    <time_frame>At 1 year post-HCT</time_frame>
    <description>Estimated by cumulative incidence methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 1 year post-HCT</time_frame>
    <description>Estimated by cumulative incidence methods.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Aggressive Non-Hodgkin Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Diffuse Large B-Cell Lymphoma</condition>
  <condition>Mantle Cell Lymphoma</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <condition>Myelodysplastic/Myeloproliferative Neoplasm</condition>
  <condition>Prolymphocytic Leukemia</condition>
  <condition>Recurrent Chronic Lymphocytic Leukemia</condition>
  <condition>Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive</condition>
  <condition>Recurrent Hodgkin Lymphoma</condition>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Recurrent Small Lymphocytic Lymphoma</condition>
  <condition>Recurrent Waldenstrom Macroglobulinemia</condition>
  <condition>Hematologic and Lymphocytic Disorder</condition>
  <condition>Blastic Plasmacytoid Dendritic Cell Neoplasm</condition>
  <arm_group>
    <arm_group_label>Arm I (mycophenolate mofetil, cyclosporine, sirolimus)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo allogeneic HCT at day 0. Patients with an HLA-matched unrelated donor receive mycophenolate mofetil PO on days 0 to 40, cyclosporine PO every 12 hours BID on days -3 to 96 then tapered to day 150, and sirolimus PO QD on days -3 to day 150 then tapered to day 180. Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and sirolimus PO QD on days -3 to 180 then tapered to day 365.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (cyclosporine, sirolimus, cyclophosphamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then tapered to day 180, and cyclophosphamide IV on days 3 and 4. Patients with an HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180, sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo HCT</description>
    <arm_group_label>Arm I (mycophenolate mofetil, cyclosporine, sirolimus)</arm_group_label>
    <arm_group_label>Arm II (cyclosporine, sirolimus, cyclophosphamide)</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 II (cyclosporine, sirolimus, cyclophosphamide)</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>Cyclosporine</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (mycophenolate mofetil, cyclosporine, sirolimus)</arm_group_label>
    <arm_group_label>Arm II (cyclosporine, sirolimus, cyclophosphamide)</arm_group_label>
    <other_name>27-400</other_name>
    <other_name>Ciclosporin</other_name>
    <other_name>CsA</other_name>
    <other_name>Cyclosporin</other_name>
    <other_name>Cyclosporin A</other_name>
    <other_name>Gengraf</other_name>
    <other_name>Neoral</other_name>
    <other_name>OL 27-400</other_name>
    <other_name>Sandimmun</other_name>
    <other_name>Sandimmune</other_name>
    <other_name>SangCya</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (mycophenolate mofetil, cyclosporine, sirolimus)</arm_group_label>
    <other_name>Cellcept</other_name>
    <other_name>MMF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (mycophenolate mofetil, cyclosporine, sirolimus)</arm_group_label>
    <arm_group_label>Arm II (cyclosporine, sirolimus, cyclophosphamide)</arm_group_label>
    <other_name>AY 22989</other_name>
    <other_name>RAPA</other_name>
    <other_name>Rapamune</other_name>
    <other_name>Rapamycin</other_name>
    <other_name>SILA 9268A</other_name>
    <other_name>WY-090217</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages &gt; 50 years with hematologic malignancies treatable by unrelated hematopoietic&#xD;
             cell transplant (HCT)&#xD;
&#xD;
          -  Ages 18-50 years with hematologic diseases treatable by allogeneic HCT who through&#xD;
             pre-existing medical conditions or prior therapy are considered to be at high risk for&#xD;
             regimen related toxicity associated with a high dose transplant&#xD;
&#xD;
          -  Ages 18-50 years with chronic lymphocytic leukemia (CLL)&#xD;
&#xD;
          -  Ages 18-50 years with hematologic diseases treatable by allogeneic HCT who refuse a&#xD;
             high-dose HCT; transplants must be approved for these inclusion criteria by the&#xD;
             principal investigator&#xD;
&#xD;
          -  The following diseases will be permitted although other diagnoses can be considered if&#xD;
             approved by PCC and the principal investigator.&#xD;
&#xD;
               -  Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse&#xD;
                  large B cell NHL- not eligible for autologous HCT, not eligible for high-dose&#xD;
                  allogeneic HCT, or after failed autologous HCT&#xD;
&#xD;
               -  Mantle cell NHL - may be treated in first complete remission (CR); (diagnostic&#xD;
                  lumbar puncture [LP] required pre-transplant)&#xD;
&#xD;
               -  Low grade NHL - with &lt; 6 month duration of CR between courses of conventional&#xD;
                  therapy&#xD;
&#xD;
               -  CLL - must have either 1) failed to meet National Cancer Institute (NCI) Working&#xD;
                  Group criteria for complete or partial response after therapy with a regimen&#xD;
                  containing fludarabine (FLU) (or another nucleoside analog, e.g. cladribine&#xD;
                  [2-CDA], pentostatin) or experience disease relapse within 12 months after&#xD;
                  completing therapy with a regimen containing FLU (or another nucleoside analog);&#xD;
                  2) failed FLU-cyclophosphamide (CY)-rituximab (FCR) combination chemotherapy at&#xD;
                  any time point; or 3) have &quot;17p deletion&quot; cytogenetic abnormality; patients&#xD;
                  should have received induction chemotherapy but could be transplanted in 1st CR;&#xD;
                  or 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or&#xD;
                  diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL&#xD;
                  or PLL; 5) patients failing to achieve a response to ibrutinib as first-line&#xD;
                  therapy; 6) patients not responding to ibrutinib, idelalisib, or venetoclax as&#xD;
                  salvage therapy or intolerant of these agents as salvage therapy due to side&#xD;
                  effects; all CLL patients must have received prior myelosuppressive chemotherapy&#xD;
&#xD;
               -  Hodgkin lymphoma - must have received and failed frontline therapy&#xD;
&#xD;
               -  Multiple myeloma - must have received prior chemotherapy; consolidation of&#xD;
                  chemotherapy by autografting prior to nonmyeloablative HCT is permitted&#xD;
&#xD;
               -  Acute myeloid leukemia (AML) - must have &lt; 5% marrow blasts at the time of&#xD;
                  transplant&#xD;
&#xD;
               -  Acute lymphocytic leukemia (ALL) - must have &lt; 5% marrow blasts at the time of&#xD;
                  transplant&#xD;
&#xD;
               -  Chronic myeloid leukemia (CML) - patients in CP1 must have failed or be&#xD;
                  intolerant of tyrosine kinase inhibitors (TKIs); patients beyond CP1 will be&#xD;
                  accepted if they have &lt; 5% marrow blasts at time of transplant&#xD;
&#xD;
               -  Myelodysplasia (MDS)/myeloproliferative syndrome (MPS)/chronic myelomonocytic&#xD;
                  leukemia (CMML) - patients must have &lt; 5% marrow blasts at time of transplant&#xD;
&#xD;
               -  Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy&#xD;
&#xD;
               -  Mixed Phenotype Acute Leukemia (MPAL) - must have &lt; 5% marrow blasts at the time&#xD;
                  of transplant.&#xD;
&#xD;
               -  Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) - must be in complete&#xD;
                  remission at the time of transplant&#xD;
&#xD;
          -  HLA-MATCHED UNRELATED DONOR: FHCRC matching allowed will be grades 1.0 to 2.1;&#xD;
             unrelated donors who are prospectively:&#xD;
&#xD;
               -  Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing;&#xD;
&#xD;
               -  Only a single allele disparity will be allowed for HLA-A, B, or C as defined by&#xD;
                  high resolution typing&#xD;
&#xD;
          -  HLA-MATCHED UNRELATED DONOR: Donors are excluded when preexisting immunoreactivity is&#xD;
             identified that would jeopardize donor hematopoietic cell engraftment; this&#xD;
             determination is based on the standard practice of the individual institution; the&#xD;
             recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match&#xD;
             is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens&#xD;
             for all patients before HCT; if the PRA shows &gt; 10% activity, then flow cytometric or&#xD;
             B and T cell cytotoxic cross matches should be obtained; the donor should be excluded&#xD;
             if any of the cytotoxic cross match assays are positive; for those patients with an&#xD;
             HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches&#xD;
             should be obtained regardless of the PRA results; a positive anti-donor cytotoxic&#xD;
             crossmatch is an absolute donor exclusion&#xD;
&#xD;
          -  HLA-MATCHED UNRELATED DONOR: Patient and donor pairs homozygous at a mismatched allele&#xD;
             in the graft rejection vector are considered a two-allele mismatch, i.e., the patient&#xD;
             is A*0101 and the donor is A*0102, and this type of mismatch is not allowed&#xD;
&#xD;
          -  HLA-MATCHED UNRELATED DONOR: Only granulocyte colony-stimulating factor (G-CSF)&#xD;
             mobilized PBSC will be permitted as a HSC source on this protocol&#xD;
&#xD;
          -  HLA-MISMATCHED UNRELATED DONOR: Unrelated volunteer donors who are mismatched with the&#xD;
             recipient within one of the following limitations:&#xD;
&#xD;
               -  Mismatch for one HLA class I antigen with or without an additional mismatch for&#xD;
                  one HLA-class I allele, but matched for HLA-DRB1 and HLA-DQ, OR&#xD;
&#xD;
               -  Mismatched for two HLA class I alleles, but matched for HLA-DRB1 and HLA-DQ&#xD;
&#xD;
               -  HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1&#xD;
                  and/or DQB1 antigen/allele mismatch&#xD;
&#xD;
          -  HLA-MISMATCHED UNRELATED DONOR: HLA-matching must be based on results of high&#xD;
             resolution typing at HLA-A, -B, -C, - DRB1, and -DQ&#xD;
&#xD;
          -  HLA-MISMATCHED UNRELATED DONOR: If the patient is homozygous at the mismatch HLA class&#xD;
             I locus or II locus, the donor must be heterozygous at that locus and one allele must&#xD;
             match the patient (i.e., patient is homozygous A*01:01 and donor is heterozygous&#xD;
             A*01:01, A*02:01); this mismatch will be considered a one-antigen mismatch for&#xD;
             rejection only&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with rapidly progressive intermediate or high grade NHL&#xD;
&#xD;
          -  Patients with a diagnosis of chronic myelomonocytic leukemia (CMML) who have not&#xD;
             received induction chemotherapy&#xD;
&#xD;
          -  Patients with MDS-EB or AML who have not received myelosuppressive chemotherapy i.e.&#xD;
             induction chemotherapy or at least 4 cycles of a venetoclax-containing regimen will be&#xD;
             excluded from Regimen B conditioning (Fludarabine and total body irradiation [TBI])&#xD;
&#xD;
          -  CNS involvement with disease refractory to intrathecal chemotherapy&#xD;
&#xD;
          -  Presence of circulating blasts determined to be associated with disease (in the blood)&#xD;
             for patients with AML, ALL or CML&#xD;
&#xD;
          -  Presence of &gt;= 5% circulating leukemic blasts (in the blood) detected by standard&#xD;
             pathology for patients with MDS/MPS/CMML&#xD;
&#xD;
          -  Fertile men or women unwilling to use contraceptive techniques during and for 12&#xD;
             months following treatment&#xD;
&#xD;
          -  Females who are pregnant or breast-feeding&#xD;
&#xD;
          -  Patients with active non-hematological malignancies (except non-melanoma skin cancers)&#xD;
             or those with non-hematological malignancies (except non-melanoma skin cancers) who&#xD;
             have been rendered with no evidence of disease, but have a greater than 20% chance of&#xD;
             having disease recurrence within 5 years; this exclusion does not apply to patients&#xD;
             with non-hematologic malignancies that do not require therapy&#xD;
&#xD;
          -  Fungal infections with radiological progression after receipt of amphotericin B or&#xD;
             active triazole for greater than 1 month&#xD;
&#xD;
          -  Organ dysfunction&#xD;
&#xD;
               -  Cardiac ejection fraction &lt; 35% (or, if unable to obtain ejection fraction,&#xD;
                  shortening fraction of &lt; 26%); ejection fraction is required if age &gt; 50 years or&#xD;
                  there is a history of anthracycline exposure or history of cardiac disease;&#xD;
                  patients with a shortening fraction &lt; 26% may be enrolled if approved by a&#xD;
                  cardiologist&#xD;
&#xD;
               -  Pulmonary:&#xD;
&#xD;
                  ** Diffusing capacity of the lungs for carbon monoxide (DLCO) &lt; 40%, forced&#xD;
                  expiratory volume in the first second of breath (FEV1) &lt; 40% and/or receiving&#xD;
                  supplementary continuous oxygen; when pulmonary function tests (PFTs) cannot be&#xD;
                  obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be&#xD;
                  used: Any patient with oxygen saturation on room air of &lt; 89% during a 6MWT will&#xD;
                  be excluded&#xD;
&#xD;
               -  The FHCRC PI of the study must approve of enrollment of all patients with&#xD;
                  pulmonary nodules&#xD;
&#xD;
          -  Liver function abnormalities: Patients with clinical or laboratory evidence of liver&#xD;
             disease would be evaluated for the cause of liver disease, its clinical severity in&#xD;
             terms of liver function, and the degree of portal hypertension; patients will be&#xD;
             excluded if they are found to have fulminant liver failure, cirrhosis of the liver&#xD;
             with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a&#xD;
             history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic&#xD;
             synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related&#xD;
             to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary&#xD;
             obstruction, chronic viral hepatitis with total serum bilirubin &gt; 3 mg/dL, or&#xD;
             symptomatic biliary disease&#xD;
&#xD;
          -  Karnofsky scores &lt; 60&#xD;
&#xD;
          -  Patient has poorly controlled hypertension and on multiple antihypertensives&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive patients&#xD;
&#xD;
          -  Active bacterial or fungal infections unresponsive to medical therapy&#xD;
&#xD;
          -  The addition of cytotoxic agents for &quot;cytoreduction&quot; with the exception of tyrosine&#xD;
             kinase inhibitors (such as imatinib), cytokine therapy, hydroxyurea, low dose&#xD;
             cytarabine, chlorambucil, or Rituxan will not be allowed within three weeks of the&#xD;
             initiation of conditioning&#xD;
&#xD;
          -  Patients on hemodialysis&#xD;
&#xD;
          -  DONOR: Donor (or centers) who will exclusively donate marrow&#xD;
&#xD;
          -  DONOR: Donors who are HIV-positive and/or, medical conditions that would result in&#xD;
             increased risk for G-CSF mobilization and harvest of peripheral blood stem cell (PBSC)&#xD;
&#xD;
          -  DONOR: Patients who are homozygous at the mismatched HLA class I or II locus, the&#xD;
             donor is excluded if homozygous at the mismatched locus (i.e., patient is homozygous A&#xD;
             *01:01 and donor is homozygous A *02:01); this type of mismatch is considered a&#xD;
             two-antigen mismatch and is not allowed&#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>Masumi Ueda Oshima</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Masumi Ueda Oshima</last_name>
    <phone>206-667-4546</phone>
    <email>mueda@fredhutch.org</email>
  </overall_contact>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Masumi Ueda Oshima</last_name>
      <phone>206-667-4546</phone>
      <email>mueda@fredhutch.org</email>
    </contact>
    <investigator>
      <last_name>Masumi Ueda Oshima</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>March 8, 2023</last_update_submitted>
  <last_update_submitted_qc>March 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 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>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Neoplasms</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, Myeloid</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Leukemia, Prolymphocytic</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Myeloproliferative Disorders</mesh_term>
    <mesh_term>Myelodysplastic-Myeloproliferative Diseases</mesh_term>
    <mesh_term>Hematologic Diseases</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclosporine</mesh_term>
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Cyclosporins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03246906
org study id: 9816
secondary id: NCI-2017-01311
secondary id: 9816
secondary id: P01CA078902
secondary id: P30CA015704
secondary id: RG9217021
nct id: NCT03246906
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase II trial includes a blood stem cell transplant from an unrelated donor
      to treat blood cancer. The treatment also includes chemotherapy drugs, but in lower doses
      than conventional (standard) stem cell transplants. The researchers will compare two
      different drug combinations used to reduce the risk of a common but serious complication
      called "graft versus host disease" (GVHD) following the transplant. Two drugs, cyclosporine
      (CSP) and sirolimus (SIR), will be combined with either mycophenolate mofetil (MMF) or
      post-transplant cyclophosphamide (PTCy). This part of the transplant procedure is the main
      research focus of the study.
OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients undergo allogeneic hematopoietic stem cell transplant (HCT) at day 0.
      Patients with an HLA-matched unrelated donor receive mycophenolate mofetil orally (PO) on
      days 0 to 40, cyclosporine PO every 12 hours twice daily (BID) on days -3 to 96 then tapered
      to day 150, and sirolimus PO once daily (QD) on days -3 to day 150 then tapered to day 180.
      Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then
      tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and
      sirolimus PO QD on days -3 to 180 then tapered to day 365.

      ARM II: Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive
      cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then
      tapered to day 180, and cyclophosphamide intravenously (IV) on days 3 and 4. Patients with an
      HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180,
      sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and
      4.

      After completion of study treatment, patients are followed up at 6 months and every year
      thereafter.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Chronic graft versus host disease (GVHD)-free, relapse-free survival (CRFS)
time frame: At 1 year post- hematopoietic cell transplantation (HCT)
description: Composite time-to-event outcome in which events include moderate or severe chronic GVHD based on National Institute of Health consensus criteria, relapse, or death from any cause.
measure: Grades II-IV and III-IV acute graft versus host disease (GVHD)
time frame: At day 100 post-HCT
description: Estimated by cumulative incidence methods. Grading is based on "Graft-vs-host disease" Sullivan, Keith M. Hematopoietic Cell Transplantation Ed: D. Thomas, K. Blume, S. Forman, Blackwell Sciences; 1999, pages 518-519.
measure: Late graft versus host disease (GVHD) not meeting National Institute of Health (NIH) consensus criteria for chronic GVHD
time frame: At 1 year post-HCT
description: GVHD occurring after day 100 and not meeting NIH consensus criteria for chronic GVHD. Estimated by cumulative incidence methods.
measure: Moderate and severe chronic graft versus host disease
time frame: At 1 year post-HCT
description: Estimated by cumulative incidence methods. Based on NIH consensus criteria.
measure: Relapse
time frame: At 1 year post-HCT
description: Estimated by cumulative incidence methods.
measure: Non-relapse mortality
time frame: At 1 year post-HCT
description: Estimated by cumulative incidence methods.
measure: Progression or relapse-free survival
time frame: At 1 year post-HCT
description: Estimated by cumulative incidence methods.
measure: Overall survival
time frame: At 1 year post-HCT
description: Estimated by cumulative incidence methods.
arm group label: Arm I (mycophenolate mofetil, cyclosporine, sirolimus)
arm group type: Experimental
description: Patients undergo allogeneic HCT at day 0. Patients with an HLA-matched unrelated donor receive mycophenolate mofetil PO on days 0 to 40, cyclosporine PO every 12 hours BID on days -3 to 96 then tapered to day 150, and sirolimus PO QD on days -3 to day 150 then tapered to day 180. Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and sirolimus PO QD on days -3 to 180 then tapered to day 365.
arm group label: Arm II (cyclosporine, sirolimus, cyclophosphamide)
arm group type: Experimental
description: Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then tapered to day 180, and cyclophosphamide IV on days 3 and 4. Patients with an HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180, sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and 4.
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo HCT
arm group label: Arm I (mycophenolate mofetil, cyclosporine, sirolimus)
arm group label: Arm II (cyclosporine, sirolimus, cyclophosphamide)
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 II (cyclosporine, sirolimus, cyclophosphamide)
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: Cyclosporine
description: Given PO
arm group label: Arm I (mycophenolate mofetil, cyclosporine, sirolimus)
arm group label: Arm II (cyclosporine, sirolimus, cyclophosphamide)
other name: 27-400
other name: Ciclosporin
other name: CsA
other name: Cyclosporin
other name: Cyclosporin A
other name: Gengraf
other name: Neoral
other name: OL 27-400
other name: Sandimmun
other name: Sandimmune
other name: SangCya
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Given PO
arm group label: Arm I (mycophenolate mofetil, cyclosporine, sirolimus)
other name: Cellcept
other name: MMF
intervention type: Drug
intervention name: Sirolimus
description: Given PO
arm group label: Arm I (mycophenolate mofetil, cyclosporine, sirolimus)
arm group label: Arm II (cyclosporine, sirolimus, cyclophosphamide)
other name: AY 22989
other name: RAPA
other name: Rapamune
other name: Rapamycin
other name: SILA 9268A
other name: WY-090217
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Masumi Ueda Oshima
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Masumi Ueda Oshima
phone: 206-667-4546
email: mueda@fredhutch.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Neoplasms
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Leukemia, Myeloid
mesh term: Lymphoma, Mantle-Cell
mesh term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Waldenstrom Macroglobulinemia
mesh term: Multiple Myeloma
mesh term: Leukemia, Prolymphocytic
mesh term: Myelodysplastic Syndromes
mesh term: Myeloproliferative Disorders
mesh term: Myelodysplastic-Myeloproliferative Diseases
mesh term: Hematologic Diseases
mesh term: Recurrence
mesh term: Cyclosporine
mesh term: Sirolimus
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Cyclosporins
sharing ipd: No