xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06013423</url>
    </required_header>
    <id_info>
      <org_study_id>RG1123652</org_study_id>
      <secondary_id>NCI-2023-05598</secondary_id>
      <secondary_id>RG1123652</secondary_id>
      <nct_id>NCT06013423</nct_id>
    </id_info>
    <brief_title>Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases</brief_title>
    <official_title>Optimized Cord Blood Transplantation for the Treatment of High-Risk Hematologic Malignancies in Adults and Pediatrics</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fred Hutchinson Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Cord Blood Network</agency>
        <agency_class>Other</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 studies how well giving an umbilical cord blood transplant together with&#xD;
        cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients&#xD;
        with hematologic diseases. Giving chemotherapy, such as cyclophosphamide, fludarabine and&#xD;
        thiotepa, and TBI before a donor cord blood transplant (CBT) helps stop the growth of cancer&#xD;
        and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem&#xD;
        cells. When the healthy stem cells from a donor are infused into the patient they may help&#xD;
        the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.&#xD;
        Sometimes the transplanted cells from a donor can make an immune response against the body's&#xD;
        normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this&#xD;
        from happening in patients with high-risk hematologic diseases.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        OUTLINE: Patients are assigned to 1 of 2 arms.&#xD;
  &#xD;
        ARM I: Patients aged 6 months through 30 years old receive myeloablative conditioning&#xD;
        comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide&#xD;
        IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on days -4 to -1. Patients&#xD;
        then undergo UCBT on day 0. Patients undergo blood sample collection throughout the study.&#xD;
        Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and diagnostic&#xD;
        imaging during screening and as clinically indicated on study. Patients also undergo blood&#xD;
        sample collection and bone marrow aspirate during screening and on study.&#xD;
  &#xD;
        ARM II: Patients aged 6 months through 65 years old receive myeloablative conditioning&#xD;
        comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6,&#xD;
        thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily (QD) on&#xD;
        days -2 and -1. Patients undergo ECHO or MUGA and diagnostic imaging during screening and as&#xD;
        clinically indicated on study. Patients also undergo blood sample collection and bone marrow&#xD;
        aspirate during screening and on study.&#xD;
  &#xD;
        Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours,&#xD;
        then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day 101.&#xD;
        Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if&#xD;
        tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered to BID on&#xD;
        day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks&#xD;
        beginning on day 45 (or 15 days after engraftment if engraftment occurred &gt; day 30) after&#xD;
        engraftment if there continues to be no evidence of acute GVHD.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up at day 180, 1 year, and 2&#xD;
        years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">October 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">October 31, 2024</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>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Overall survival</measure>
      <time_frame>At 1 year</time_frame>
      <description>Will be assessed after optimized cord blood transplant (CBT) in adults and children with hematologic malignancies. Will be calculated using the Kaplan-Meier method.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cumulative incidence of neutrophil and platelet engraftment</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be calculated within the competing risks framework considering death without neutrophil or platelet recovery, respectively, as completing events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidences of graft failure</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be calculated within the competing risks framework considering death without engraftment before day 21 as a competing event.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of grade II-IV and III-IV acute graft-versus-host disease (aGVHD)</measure>
      <time_frame>At day 100</time_frame>
      <description>Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of grade II-IV and III-IV aGVHD</measure>
      <time_frame>At day 180</time_frame>
      <description>Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of chronic graft-versus-host disease (cGVHD)</measure>
      <time_frame>At 1, 2 and 3 years</time_frame>
      <description>Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Organ distribution of GVHD</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be calculated within the competing risks framework considering death without neutrophil or platelet recovery, respectively, as completing events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be assessed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to immunosuppression cessation</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be assessed using CTCAE v 5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pattern of donor chimerism</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be assessed using CTCAE v 5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of pre-engraftment syndrome (PES)</measure>
      <time_frame>Up to 1 year</time_frame>
      <description>Will be assessed using CTCAE v 5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of transplant related mortality (TRM)</measure>
      <time_frame>At 100 days, 6 months, 1 and 2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of relapse</measure>
      <time_frame>At 1, and 2 years after CBT</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">54</enrollment>
    <condition>Acute Leukemia of Ambiguous Lineage</condition>
    <condition>Acute Lymphoblastic Leukemia</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>Blastic Plasmacytoid Dendritic Cell Neoplasm</condition>
    <condition>Hematopoietic and Lymphoid System Neoplasm</condition>
    <condition>Mixed Phenotype Acute Leukemia</condition>
    <condition>Myelodysplastic Syndrome</condition>
    <condition>Myeloproliferative Neoplasm</condition>
    <condition>Non-Hodgkin Lymphoma</condition>
    <arm_group>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>See detailed description.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>See detailed description.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Marrow Aspirate</intervention_name>
      <description>Undergo bone marrow aspirate</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>BONE MARROW, LIQUID</other_name>
      <other_name>Human Bone Marrow Aspirate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>Receive IV</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</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>Cyclophosphamide 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>Receive IV or PO</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</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>Cyclosporine Modified</other_name>
      <other_name>Gengraf</other_name>
      <other_name>Neoral</other_name>
      <other_name>OL 27-400</other_name>
      <other_name>Sandimmune</other_name>
      <other_name>SangCya</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Diagnostic Imaging</intervention_name>
      <description>Undergo diagnostic imaging</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>Medical Imaging</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Echocardiography</intervention_name>
      <description>Undergo ECHO</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>EC</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine Phosphate</intervention_name>
      <description>Receive IV</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</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>Procedure</intervention_type>
      <intervention_name>Multigated Acquisition Scan</intervention_name>
      <description>Undergo MUGA</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>Blood Pool Scan</other_name>
      <other_name>Equilibrium Radionuclide Angiography</other_name>
      <other_name>Gated Blood Pool Imaging</other_name>
      <other_name>Gated Heart Pool Scan</other_name>
      <other_name>MUGA</other_name>
      <other_name>MUGA Scan</other_name>
      <other_name>Multi-Gated Acquisition Scan</other_name>
      <other_name>Radionuclide Ventriculogram Scan</other_name>
      <other_name>Radionuclide Ventriculography</other_name>
      <other_name>RNVG</other_name>
      <other_name>SYMA Scanning</other_name>
      <other_name>Synchronized Multigated Acquisition Scanning</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mycophenolate Mofetil</intervention_name>
      <description>Receive IV</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>CellCept</other_name>
      <other_name>MMF</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Survey Administration</intervention_name>
      <description>Ancillary studies</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Thiotepa</intervention_name>
      <description>Receive IV</description>
      <arm_group_label>Arm II (myeloablative UCBT)</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 high-dose or middle-intensity TBI</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>SCT_TBI</other_name>
      <other_name>TBI</other_name>
      <other_name>Total Body Irradiation</other_name>
      <other_name>Whole Body</other_name>
      <other_name>Whole Body Irradiation</other_name>
      <other_name>Whole-Body Irradiation</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Umbilical Cord Blood Transplantation</intervention_name>
      <description>Undergo UCBT</description>
      <arm_group_label>Arm I (myeloablative UCBT)</arm_group_label>
      <arm_group_label>Arm II (myeloablative UCBT)</arm_group_label>
      <other_name>Cord Blood</other_name>
      <other_name>Cord Blood Transplantation</other_name>
      <other_name>UCB transplantation</other_name>
      <other_name>UMBILICAL CORD BLOOD TRANSPLANT</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients aged 6 months to =&lt; 65 years at time of consent.&#xD;
  &#xD;
            -  Acute myelogenous leukemia (AML):&#xD;
  &#xD;
                 -  Complete first remission (CR1), complete second remission (CR2) or greater (CR2+)&#xD;
                    must have &lt; 5% marrow blasts at the time of transplant.&#xD;
  &#xD;
                 -  Patients in morphologic remission with persistent cytogenetic, flow cytometric,&#xD;
                    or molecular aberrations are eligible.&#xD;
  &#xD;
            -  Acute lymphoblastic leukemia (ALL):&#xD;
  &#xD;
                 -  Complete first remission (CR1) at high risk for relapse such as any of the&#xD;
                    following:&#xD;
  &#xD;
                      -  Presence of any high-risk cytogenetic abnormalities such as t(9;22),&#xD;
                         t(1;19), t(4;11) or other MLL rearrangements (11q23) or other high-risk&#xD;
                         molecular abnormality.&#xD;
  &#xD;
                      -  Failure to achieve MRD- complete remission after induction therapy.&#xD;
  &#xD;
                      -  Persistence or recurrence of minimal residual disease on therapy.&#xD;
  &#xD;
                      -  Any patient unable to tolerate consolidation and/or maintenance chemotherapy&#xD;
                         as would have been deemed appropriate by the treating physician.&#xD;
  &#xD;
                      -  Other high-risk features not defined above.&#xD;
  &#xD;
                 -  Complete second remission (CR2) or greater (CR2+).&#xD;
  &#xD;
                      -  Note: ALL with less than 5% blasts at time of transplant but persistent&#xD;
                         cytogenetic, flow cytometric or molecular aberrations are eligible.&#xD;
  &#xD;
            -  Other acute leukemias: Acute leukemias of ambiguous lineage or mixed phenotype with&#xD;
               less than 5% blasts. Leukemias in morphologic remission with persistent cytogenetic,&#xD;
               flow cytometric or molecular aberrations are eligible.&#xD;
  &#xD;
            -  Chronic Myeloid Leukemia (CML): Excluding refractory blast crisis. To be eligible in&#xD;
               first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase&#xD;
               inhibitor therapy.&#xD;
  &#xD;
            -  Myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) other than&#xD;
               myelofibrosis:&#xD;
  &#xD;
                 -  MDS/MPD overlap syndromes without myelofibrosis.&#xD;
  &#xD;
                 -  MDS/ MPD patients must have less than 10% bone marrow myeloblasts and absolute&#xD;
                    neutrophil count (ANC) &gt; 0.2 (growth factor supported if necessary) at transplant&#xD;
                    work-up.&#xD;
  &#xD;
            -  Non-Hodgkin lymphoma (NHL) at high-risk of relapse or progression if not in remission:&#xD;
  &#xD;
                 -  Eligible patients with aggressive histology (such as, but not limited to, diffuse&#xD;
                    large B-cell NHL, mantle cell NHL, and T-cell histology) in CR by PET/CT imaging.&#xD;
  &#xD;
                 -  Eligible patients with indolent B-cell NHL (such as, but not limited to,&#xD;
                    follicular, small cell or marginal zone NHL) will have 2nd or subsequent&#xD;
                    progression with PR or CR by PET/CT imaging.&#xD;
  &#xD;
            -  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) in morphologic remission.&#xD;
  &#xD;
            -  Only for adult patients, to prevent graft rejection, patients who received only&#xD;
               non-lymphodepleting agents for their malignancy (hypomethylating agents, venetoclax,&#xD;
               hydroxyurea, TKIs etc.), or patients who received lymphodepleting chemotherapy &gt; 3&#xD;
               months prior to scheduled admission, may receive fludarabine 25 mg/m^2 daily x 3 days&#xD;
               for lymphodepletion 14-42 days (aiming for 2-4 weeks) at the discretion of the&#xD;
               principal investigator (PI).&#xD;
  &#xD;
            -  For patients &gt; 18 years old, Karnofsky score equal or greater than 70%. For patients&#xD;
               =&lt; 18 years old, Lansky score equal to or greater than 50%.&#xD;
  &#xD;
            -  Calculated creatinine clearance &gt; 70 ml/min.&#xD;
  &#xD;
            -  Bilirubin &lt; 1.5 mg/dL (unless benign congenital hyperbilirubinemia or hemolysis).&#xD;
  &#xD;
            -  Alanine transaminase (ALT) &lt; 3 x upper limit of normal (ULN).&#xD;
  &#xD;
            -  For patients &gt; 18 years old, pulmonary function (spirometry and corrected diffusing&#xD;
               capacity for carbon monoxide [DLCO]) &gt; 60% predicted. For patients =&lt; 18 years old, or&#xD;
               any patient unable to perform pulmonary function tests, O2 saturation &gt; 92% on room&#xD;
               air.&#xD;
  &#xD;
            -  Left ventricular ejection fraction &gt; 50%.&#xD;
  &#xD;
            -  Albumin &gt; 3.0 g/dL.&#xD;
  &#xD;
            -  For patients &gt; 18 years old, Hematopoietic Cell Transplantation Comorbidity index&#xD;
               (HCT-CI) =&lt; 5.&#xD;
  &#xD;
            -  UCB units will be selected according to current umbilical cord blood graft selection&#xD;
               algorithm. One or two UCB units may be used to achieve the required cell dose.&#xD;
  &#xD;
            -  The UCB graft is matched at 4-6 HLA-A, B, DRB1 antigens with the recipient. This may&#xD;
               include 0-2 antigen mismatches at the A or B or DRB1 loci. Unit selection based on&#xD;
               cryopreserved nucleated cell dose and HLA-A, B, DRB1 using intermediate resolution A,&#xD;
               B antigen and DRB1 allele typing.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow&#xD;
               fibrosis.&#xD;
  &#xD;
            -  Patients persistent with central nervous system (CNS) involvement in cerebrospinal&#xD;
               fluid (CSF) or CNS imaging at time of screening0&#xD;
  &#xD;
            -  Prior checkpoint inhibitors/ blockade in the last 12 months.&#xD;
  &#xD;
            -  Two prior stem cell transplants of any kind.&#xD;
  &#xD;
            -  One prior autologous stem cell transplant within the preceding 12 months.&#xD;
  &#xD;
            -  Prior allogeneic transplantation.&#xD;
  &#xD;
            -  Prior involved field radiation therapy that would preclude safe delivery of 400cGy&#xD;
               total body irradiation (TBI) in the opinion of radiation oncology.&#xD;
  &#xD;
            -  Active and uncontrolled infection at time of transplantation.&#xD;
  &#xD;
            -  HIV infection.&#xD;
  &#xD;
            -  Inadequate performance status/ organ function.&#xD;
  &#xD;
            -  Pregnancy or breast feeding.&#xD;
  &#xD;
            -  Patient or guardian unable to give informed consent or unable to comply with the&#xD;
               treatment protocol including appropriate supportive care, long-term follow-up, and&#xD;
               research tests.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Months</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ann Dahlberg</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ann Dahlberg</last_name>
      <phone>206-667-1959</phone>
      <email>adahlber@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>
      <contact>
        <last_name>Ann Dahlberg</last_name>
        <phone>206-667-1959</phone>
        <email>adahlber@fredhutch.org</email>
      </contact>
      <investigator>
        <last_name>Ann Dahlberg</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 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>Neoplasms</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
      <mesh_term>Myelodysplastic Syndromes</mesh_term>
      <mesh_term>Myeloproliferative Disorders</mesh_term>
      <mesh_term>Acute Disease</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cyclosporine</mesh_term>
      <mesh_term>Mycophenolic Acid</mesh_term>
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Thiotepa</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Fludarabine phosphate</mesh_term>
      <mesh_term>Cyclosporins</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06013423
  org study id: RG1123652
  secondary id: NCI-2023-05598
  secondary id: RG1123652
  nct id: NCT06013423
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase II trial studies how well giving an umbilical cord blood transplant together with
        cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients
        with hematologic diseases. Giving chemotherapy, such as cyclophosphamide, fludarabine and
        thiotepa, and TBI before a donor cord blood transplant (CBT) helps stop the growth of cancer
        and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem
        cells. When the healthy stem cells from a donor are infused into the patient they may help
        the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
        Sometimes the transplanted cells from a donor can make an immune response against the body's
        normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this
        from happening in patients with high-risk hematologic diseases.
  OUTLINE: Patients are assigned to 1 of 2 arms.
  
        ARM I: Patients aged 6 months through 30 years old receive myeloablative conditioning
        comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide
        IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on days -4 to -1. Patients
        then undergo UCBT on day 0. Patients undergo blood sample collection throughout the study.
        Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and diagnostic
        imaging during screening and as clinically indicated on study. Patients also undergo blood
        sample collection and bone marrow aspirate during screening and on study.
  
        ARM II: Patients aged 6 months through 65 years old receive myeloablative conditioning
        comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6,
        thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily (QD) on
        days -2 and -1. Patients undergo ECHO or MUGA and diagnostic imaging during screening and as
        clinically indicated on study. Patients also undergo blood sample collection and bone marrow
        aspirate during screening and on study.
  
        Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours,
        then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day 101.
        Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if
        tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered to BID on
        day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks
        beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after
        engraftment if there continues to be no evidence of acute GVHD.
  
        After completion of study treatment, patients are followed up at day 180, 1 year, and 2
        years.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall survival
  time frame: At 1 year
  description: Will be assessed after optimized cord blood transplant (CBT) in adults and children with hematologic malignancies. Will be calculated using the Kaplan-Meier method.
  measure: Cumulative incidence of neutrophil and platelet engraftment
  time frame: Up to 1 year
  description: Will be calculated within the competing risks framework considering death without neutrophil or platelet recovery, respectively, as completing events
  measure: Incidences of graft failure
  time frame: Up to 1 year
  description: Will be calculated within the competing risks framework considering death without engraftment before day 21 as a competing event.
  measure: Incidence of grade II-IV and III-IV acute graft-versus-host disease (aGVHD)
  time frame: At day 100
  description: Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.
  measure: Incidence of grade II-IV and III-IV aGVHD
  time frame: At day 180
  description: Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.
  measure: Incidence of chronic graft-versus-host disease (cGVHD)
  time frame: At 1, 2 and 3 years
  description: Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.
  measure: Organ distribution of GVHD
  time frame: Up to 1 year
  description: Will be calculated within the competing risks framework considering death without neutrophil or platelet recovery, respectively, as completing events
  measure: Incidence of adverse events
  time frame: Up to 1 year
  description: Will be assessed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).
  measure: Time to immunosuppression cessation
  time frame: Up to 1 year
  description: Will be assessed using CTCAE v 5.0.
  measure: Pattern of donor chimerism
  time frame: Up to 1 year
  description: Will be assessed using CTCAE v 5.0.
  measure: Incidence of pre-engraftment syndrome (PES)
  time frame: Up to 1 year
  description: Will be assessed using CTCAE v 5.0.
  measure: Incidence of transplant related mortality (TRM)
  time frame: At 100 days, 6 months, 1 and 2 years
  measure: Incidence of relapse
  time frame: At 1, and 2 years after CBT
  arm group label: Arm I (myeloablative UCBT)
  arm group type: Experimental
  description: See detailed description.
  arm group label: Arm II (myeloablative UCBT)
  arm group type: Experimental
  description: See detailed description.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Bone Marrow Aspirate
  description: Undergo bone marrow aspirate
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: BONE MARROW, LIQUID
  other name: Human Bone Marrow Aspirate
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: Receive IV
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  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: Cyclophosphamide 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: Receive IV or PO
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: 27-400
  other name: Ciclosporin
  other name: CsA
  other name: Cyclosporin
  other name: Cyclosporin A
  other name: Cyclosporine Modified
  other name: Gengraf
  other name: Neoral
  other name: OL 27-400
  other name: Sandimmune
  other name: SangCya
  intervention type: Procedure
  intervention name: Diagnostic Imaging
  description: Undergo diagnostic imaging
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: Medical Imaging
  intervention type: Procedure
  intervention name: Echocardiography
  description: Undergo ECHO
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: EC
  intervention type: Drug
  intervention name: Fludarabine Phosphate
  description: Receive IV
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  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: Procedure
  intervention name: Multigated Acquisition Scan
  description: Undergo MUGA
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: Blood Pool Scan
  other name: Equilibrium Radionuclide Angiography
  other name: Gated Blood Pool Imaging
  other name: Gated Heart Pool Scan
  other name: MUGA
  other name: MUGA Scan
  other name: Multi-Gated Acquisition Scan
  other name: Radionuclide Ventriculogram Scan
  other name: Radionuclide Ventriculography
  other name: RNVG
  other name: SYMA Scanning
  other name: Synchronized Multigated Acquisition Scanning
  intervention type: Drug
  intervention name: Mycophenolate Mofetil
  description: Receive IV
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: CellCept
  other name: MMF
  intervention type: Other
  intervention name: Survey Administration
  description: Ancillary studies
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  intervention type: Drug
  intervention name: Thiotepa
  description: Receive IV
  arm group label: Arm II (myeloablative UCBT)
  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 high-dose or middle-intensity TBI
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: SCT_TBI
  other name: TBI
  other name: Total Body Irradiation
  other name: Whole Body
  other name: Whole Body Irradiation
  other name: Whole-Body Irradiation
  intervention type: Procedure
  intervention name: Umbilical Cord Blood Transplantation
  description: Undergo UCBT
  arm group label: Arm I (myeloablative UCBT)
  arm group label: Arm II (myeloablative UCBT)
  other name: Cord Blood
  other name: Cord Blood Transplantation
  other name: UCB transplantation
  other name: UMBILICAL CORD BLOOD TRANSPLANT
  criteria: 
  gender: All
  minimum age: 6 Months
  maximum age: 65 Years
  healthy volunteers: No
  last name: Ann Dahlberg
  role: Principal Investigator
  affiliation: Fred Hutch/University of Washington Cancer Consortium
  last name: Ann Dahlberg
  phone: 206-667-1959
  email: adahlber@fredhutch.org
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Neoplasms
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Myelodysplastic Syndromes
  mesh term: Myeloproliferative Disorders
  mesh term: Acute Disease
  mesh term: Cyclosporine
  mesh term: Mycophenolic Acid
  mesh term: Cyclophosphamide
  mesh term: Thiotepa
  mesh term: Fludarabine
  mesh term: Fludarabine phosphate
  mesh term: Cyclosporins
  sharing ipd: No