<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/NCT03779854</url>
  </required_header>
  <id_info>
    <org_study_id>RG1003345</org_study_id>
    <secondary_id>9880</secondary_id>
    <secondary_id>NCI-2018-01752</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG1003345</secondary_id>
    <secondary_id>P01CA018029-43</secondary_id>
    <nct_id>NCT03779854</nct_id>
  </id_info>
  <brief_title>Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant</brief_title>
  <official_title>Multi-Center Phase II Randomized Controlled Trial of Naïve T Cell Depletion for Prevention of Chronic Graft-Versus-Host Disease in Children and Young Adults</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>
  </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 naive T-cell depletion works in preventing chronic&#xD;
      graft-versus-host disease in children and young adults with blood cancers undergoing donor&#xD;
      stem cell transplant. Sometimes the transplanted white blood cells from a donor attack the&#xD;
      body's normal tissues (called graft versus host disease). Removing a particular type of T&#xD;
      cell (naive T cells) from the donor cells before the transplant may stop this from happening.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients are randomized to 1 of 2 arms. All patients receive 1 of 3 conditioning regimens.&#xD;
&#xD;
      CONDITIONING REGIMEN A: Patients undergo total body irradiation (TBI) twice daily (BID) on&#xD;
      days -10 to -7, then receive thiotepa intravenously (IV) over 3 hours once daily (QD) on days&#xD;
      -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.&#xD;
&#xD;
      CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine&#xD;
      IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and&#xD;
      -2.&#xD;
&#xD;
      CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2,&#xD;
      busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on&#xD;
      day -1.&#xD;
&#xD;
      ARM I: Patients receive naive T-cell depleted PBSCs on day 0.&#xD;
&#xD;
      ARM II: Patients receive unmanipulated T cell-replete BM on day 0.&#xD;
&#xD;
      GVHD PROPHYLAXIS: All patients receive tacrolimus IV on days -1 to +50 followed by a taper in&#xD;
      the absence of grade II-IV aGVHD. Patients also receive methotrexate IV on days +1, +3, +6,&#xD;
      and +11.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 29, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility achievement</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Success defined as achievement of cell selection goals for two consecutive Naive T cells (TN)-depleted peripheral blood stem cells (PBSC) hematopoietic cell transplantation (HCTs) at each study site (Feasibility)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Engraftment of neutrophils by day 28 (Feasibility)</measure>
    <time_frame>At day 28</time_frame>
    <description>Success defined as achievement neutrophil engraftment (absolute neutrophil count [ANC] &gt;= 500/mm^3) on first day of three consecutive laboratory values obtained on different days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Current-graft versus host disease (GVHD)-free, relapse-free survival (Randomized Controlled Trial [RCT])</measure>
    <time_frame>At 1 year</time_frame>
    <description>Defined as alive, no relapse after HCT, no current GVHD requiring prednisone, no graft rejection or graft failure. The proportion of subjects meeting the primary endpoint will be described in each arm with 90% confidence intervals (CI) and compared between arms using the chi-square test. A two-sided 10% significance level will be used for this comparison.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Chronic GVHD (cGVHD) meeting National Institutes of Health (NIH) criteria and requiring prednisone (RCT)</measure>
    <time_frame>At 1 and 2 years</time_frame>
    <description>Cumulative incidence curve will be computed for each arm along with a 90% CI at 1 year and 2 years post-HCT. Death and/or relapse prior to occurrence of cGVHD will be considered as competing risks. The cumulative incidence curves will be compared between arms using Gray's test. The maximum severity of cGVHD will also be described in each arm and compared using the chi-squared test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD (RCT)</measure>
    <time_frame>At 3, 6, 9, 12, 15, 18, 21 and 24 months post HCT</time_frame>
    <description>Proportions of subjects alive without requiring use of prednisone (or equivalent systemic corticosteroid) for GVHD will be estimated with 90% CI for both arms at time points over 24 months, and compared using the chi-squared test.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">68</enrollment>
  <condition>Acute Biphenotypic Leukemia</condition>
  <condition>Acute Leukemia</condition>
  <condition>Acute Leukemia of Ambiguous Lineage</condition>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Acute Undifferentiated Leukemia</condition>
  <condition>Allogeneic Hematopoietic Stem Cell Transplantation Recipient</condition>
  <condition>Blastic Plasmacytoid Dendritic Cell Neoplasm</condition>
  <condition>Blasts Under 25 Percent of Bone Marrow Nucleated Cells</condition>
  <condition>Blasts Under 5 Percent of Bone Marrow Nucleated Cells</condition>
  <condition>Mixed Phenotype Acute Leukemia</condition>
  <condition>Myelodysplastic Syndrome With Excess Blasts-1</condition>
  <condition>Myelodysplastic Syndrome/Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.&#xD;
CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2.&#xD;
CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1.&#xD;
TRANSPLANT: Patients receive naive T-cell depleted PBSCs on day 0.&#xD;
GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.&#xD;
CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2.&#xD;
CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1.&#xD;
TRANSPLANT: Patients receive unmanipulated T cell-replete BM on day 0.&#xD;
GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total-Body Irradiation</intervention_name>
    <description>Undergo TBI</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <other_name>Total Body Irradiation</other_name>
    <other_name>Whole-Body Irradiation</other_name>
    <other_name>SCT_TBI</other_name>
    <other_name>TBI</other_name>
    <other_name>Whole Body Irradiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiotepa</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <other_name>1,1',1&quot;-phosphinothioylidynetrisaziridine</other_name>
    <other_name>Oncotiotepa</other_name>
    <other_name>STEPA</other_name>
    <other_name>Tepadina</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>triethylenethiophosphoramide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <other_name>2-Fluoro-9-beta-arabinofuranosyladenine</other_name>
    <other_name>2-Fluorovidarabine</other_name>
    <other_name>Fluradosa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <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>Cycloblastin</other_name>
    <other_name>Cytophosphane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <other_name>Bussulfam</other_name>
    <other_name>Busulfanum</other_name>
    <other_name>Busulfex</other_name>
    <other_name>Busulphan</other_name>
    <other_name>Misulban</other_name>
    <other_name>Misulfan</other_name>
    <other_name>Mitosan</other_name>
    <other_name>Myeleukon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Bone Marrow Transplantation</intervention_name>
    <description>Receive unmanipulated T cell replete BM</description>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <other_name>Allo BMT</other_name>
    <other_name>Allogeneic Blood and Marrow Transplantation</other_name>
    <other_name>Allogeneic BMT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</arm_group_label>
    <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>Methotrexate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
    <arm_group_label>Arm II (chemotherapy, unmanipulated T cell replete BM)</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>Emtexate</other_name>
    <other_name>Emthexat</other_name>
    <other_name>Emthexate</other_name>
    <other_name>Farmitrexat</other_name>
    <other_name>Medsatrexate</other_name>
    <other_name>Methoblastin</other_name>
    <other_name>Rheumatrex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Receive naive T-cell depleted PBSCs</description>
    <arm_group_label>Arm I (chemotherapy, naive T-cell depleted PBSC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient must have one of the following diagnoses and be considered to be an&#xD;
             appropriate candidate for allogeneic HCT by the study site principal investigator&#xD;
             (PI):&#xD;
&#xD;
               -  Acute lymphoblastic leukemia (ALL) with &lt; 5% marrow blasts.&#xD;
&#xD;
               -  Acute myeloid leukemia (AML) with &lt; 25% marrow blasts.&#xD;
&#xD;
               -  Other acute leukemia (OAL) including but not limited to acute biphenotypic&#xD;
                  leukemia (ABL), ambiguous lineage (ALAL), mixed phenotype acute leukemia (MPAL),&#xD;
                  blastic plasmacytoid dendritic cell neoplasm (BPDCN), and acute undifferentiated&#xD;
                  leukemia (AUL) with &lt; 5% marrow blasts.&#xD;
&#xD;
               -  Myelodysplastic syndrome (MDS) with excess blasts (EB-1 and EB-2) and has&#xD;
                  received cytotoxic induction chemotherapy.&#xD;
&#xD;
          -  Age 6 months to 22 years at the time informed consent.&#xD;
&#xD;
          -  Matched related donor (MRD) or matched unrelated donor (MUD) (defined as 8/8 match for&#xD;
             human leukocyte antigen [HLA]-A, -B, -C, -DRB1).&#xD;
&#xD;
          -  Planned product type for infusion is PBSC or BM (i.e. not cord blood):&#xD;
&#xD;
               -  For feasibility phase, planned product type for infusion must be PBSC.&#xD;
&#xD;
               -  For RCT, planned product type must be PBSC or BM.&#xD;
&#xD;
          -  Karnofsky or Lansky score &gt;= 60%.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) at rest &gt;= 40%.&#xD;
&#xD;
          -  Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for hemoglobin)&#xD;
             &gt;= 60% predicted by pulmonary function tests (PFTs)&#xD;
&#xD;
             * Patients who are unable to perform PFTs (age &lt; 6 years or considered developmentally&#xD;
             incapable of PFTs): oxygen saturation (by oximetry) must be &gt;= 92% on room air.&#xD;
&#xD;
          -  Total bilirubin =&lt; 2 x upper limit of normal (ULN) (unless value[s] &gt; 2 x ULN are&#xD;
             disease- or medication-related).&#xD;
&#xD;
             * If value(s) are &gt; 2 x ULN and not disease- or medication related, patient must be&#xD;
             evaluated by a gastrointestinal (GI) physician. If GI physician considers protocol&#xD;
             treatment to be contraindicated for the patient, the patient will not be eligible for&#xD;
             the study.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =&lt; 2 x ULN (unless&#xD;
             value[s] &gt; 2 x ULN are disease- or medication-related).&#xD;
&#xD;
             * If value(s) are &gt; 2 x ULN and not disease- or medication related, patient must be&#xD;
             evaluated by a gastrointestinal GI physician. If GI physician considers protocol&#xD;
             treatment to be contraindicated for the patient, the patient will not be eligible for&#xD;
             the study.&#xD;
&#xD;
          -  Serum creatinine (SCr) within normal range for age. If SCr is outside normal range for&#xD;
             age, creatinine clearance (CrCl) &gt; 40 mL/min/1.73m^2 must be obtained (measured by&#xD;
             24-hour [hr] urine specimen or nuclear glomerular filtration rate [GFR]).&#xD;
&#xD;
               -  Age (Years): Maximum SCr (mg/dL)&#xD;
&#xD;
               -  =&lt; 5: 0.8&#xD;
&#xD;
               -  6-10: 1&#xD;
&#xD;
               -  11-15: 1.2&#xD;
&#xD;
               -  &gt; 15: 1.5&#xD;
&#xD;
          -  Recipient informed consent/assent/legal guardian permission documentation must be&#xD;
             obtained.&#xD;
&#xD;
          -  DONOR: May be related (MRD) or unrelated (MUD) to the subject.&#xD;
&#xD;
          -  DONOR: Must be matched to the subject at 8/8 HLA alleles (HLA-A, -B, -C, and -DRB1)&#xD;
&#xD;
          -  DONOR: Be &gt;=14 years of age.&#xD;
&#xD;
          -  DONOR: Must be available to donate in the United States of America (USA) (i.e.&#xD;
             excludes international donors).&#xD;
&#xD;
          -  DONOR: Must agree to donate BM or PBSC (i.e. agree to donate whichever product type is&#xD;
             requested) (applicable only to the RCT phase of this study).&#xD;
&#xD;
          -  DONOR: MUDs:&#xD;
&#xD;
               -  Must give informed consent according to applicable National Marrow Donor Program&#xD;
                  (NMDP) donor regulatory requirements&#xD;
&#xD;
               -  Must meet eligibility criteria as defined by the NMDP or be ineligible with&#xD;
                  statement of urgent medical need (exception 21 CFR 1271.65(b)(iii))&#xD;
&#xD;
                    -  Tests must be performed using Food and Drug Administration (FDA) licensed,&#xD;
                       cleared, and approved test kits in a Clinical Laboratory Improvement&#xD;
                       Amendments (CLIA)-certified laboratory&#xD;
&#xD;
          -  DONOR: MRDs:&#xD;
&#xD;
               -  Must be negative for human immunodeficiency virus (HIV)-1, HIV-2, human&#xD;
                  T-lymphotropic virus (HTLV)-1, HTLV-2, hepatitis B, hepatitis C (serological&#xD;
                  and/or nucleic acid testing [NAT] and/or other approved testing)&#xD;
&#xD;
               -  Must meet institutional donor eligibility criteria, or be ineligible with&#xD;
                  statement that the donor is a first or second degree relative (exception 21 CRF&#xD;
                  1271.65(b)(i)).&#xD;
&#xD;
                    -  Tests must be performed using FDA licensed, cleared, and approved test kits&#xD;
                       in a CLIA-certified laboratory.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active central nervous system (CNS) disease. A patient may have a history of CNS&#xD;
             disease; however, any CNS disease must be cleared by the end of the pre-conditioning&#xD;
             evaluation. If CNS disease is identified on the first cerebrospinal fluid (CSF)&#xD;
             evaluation within 30 days of the start of the preparative regimen, a repeat CSF&#xD;
             evaluation must be performed and show no evidence of disease in order for the patient&#xD;
             to be eligible for the protocol.&#xD;
&#xD;
          -  Patients on other experimental protocols for the prevention of GVHD.&#xD;
&#xD;
          -  Patient body weight:&#xD;
&#xD;
               -  Matched related donor (MRD): &gt; 100 kg are ineligible&#xD;
&#xD;
               -  Matched unrelated donor (MUD): &gt; 75 kg must be discussed with the protocol&#xD;
                  principal investigator (PI) prior to enrollment.&#xD;
&#xD;
          -  HIV-positive.&#xD;
&#xD;
          -  Uncontrolled infections must be evaluated by an infectious disease physician and&#xD;
             considered suitable to undergo HCT by the study site PI, infectious disease physician&#xD;
             and protocol PI. Upper respiratory tract infection (URI) does not constitute an&#xD;
             uncontrolled infection in this context.&#xD;
&#xD;
          -  Life expectancy &lt; 3 months from disease other than acute leukemia or myelodysplastic&#xD;
             syndrome (MDS).&#xD;
&#xD;
          -  Significant medical condition that would make recipient unsuitable for HCT.&#xD;
&#xD;
          -  Prior allogeneic or autologous HCT.&#xD;
&#xD;
          -  Females who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Patients of child bearing age who are presumed to be fertile and are unwilling to use&#xD;
             an effective birth control method or refrain from sexual intercourse during study&#xD;
             treatment and for 12 months following HCT.&#xD;
&#xD;
          -  Known hypersensitivity to tacrolimus, fludarabine, or methotrexate (MTX).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>22 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>
  <overall_contact>
    <last_name>Marie Bleakley</last_name>
    <phone>206-667-6572</phone>
    <email>mbleakle@fredhutch.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Children's Hospital of Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ashley Gray</last_name>
      <phone>323-361-3530</phone>
      <email>agray@chla.usc.edu</email>
    </contact>
    <investigator>
      <last_name>Ashley Gray</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>200100</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Benjamin Watkins</last_name>
      <phone>404-785-1272</phone>
      <email>Benjamin.watkins@choa.org</email>
    </contact>
    <investigator>
      <last_name>Benjamin Watkins</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rajat Sharma</last_name>
      <phone>319-356-2405</phone>
      <email>rajat-sharma@uiowa.edu</email>
    </contact>
    <investigator>
      <last_name>Rajat Sharma</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber / Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Susanne Baumeister</last_name>
      <phone>617-632-4687</phone>
      <email>susanne_baumeister@dfci.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Susanne Baumeister</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UH Rainbow Babies and Children's Hospital (University Hospitals Cleveland Medical Center)</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mari Dallas</last_name>
      <phone>216-844-3345</phone>
      <email>mari.dallas@uhhospitals.org</email>
    </contact>
    <investigator>
      <last_name>Mari Dallas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rabi Hanna</last_name>
      <phone>216-444-0663</phone>
      <email>HANNAR2@ccf.org</email>
    </contact>
    <investigator>
      <last_name>Rabi Hanna</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Eneida Nemecek</last_name>
      <phone>503-494-5675</phone>
      <email>nemeceke@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Eneida Nemecek</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessie Barnum</last_name>
      <email>jessie.barnum@chp.edu</email>
    </contact>
    <investigator>
      <last_name>Jessie Barnum</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie Bleakley</last_name>
      <phone>206-667-7746</phone>
      <email>mbleakle@fredhutch.org</email>
    </contact>
    <investigator>
      <last_name>Marie Bleakley</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>September 7, 2023</last_update_submitted>
  <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 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>Preleukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Biphenotypic, Acute</mesh_term>
    <mesh_term>Bronchiolitis Obliterans Syndrome</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Anemia, Refractory, with Excess of Blasts</mesh_term>
    <mesh_term>Graft vs Host Disease</mesh_term>
    <mesh_term>Syndrome</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>Vidarabine</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Busulfan</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>
  <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/NCT03779854
org study id: RG1003345
secondary id: 9880
secondary id: NCI-2018-01752
secondary id: P30CA015704
secondary id: RG1003345
secondary id: P01CA018029-43
nct id: NCT03779854
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well naive T-cell depletion works in preventing chronic
      graft-versus-host disease in children and young adults with blood cancers undergoing donor
      stem cell transplant. Sometimes the transplanted white blood cells from a donor attack the
      body's normal tissues (called graft versus host disease). Removing a particular type of T
      cell (naive T cells) from the donor cells before the transplant may stop this from happening.
Patients are randomized to 1 of 2 arms. All patients receive 1 of 3 conditioning regimens.

      CONDITIONING REGIMEN A: Patients undergo total body irradiation (TBI) twice daily (BID) on
      days -10 to -7, then receive thiotepa intravenously (IV) over 3 hours once daily (QD) on days
      -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.

      CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine
      IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and
      -2.

      CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2,
      busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on
      day -1.

      ARM I: Patients receive naive T-cell depleted PBSCs on day 0.

      ARM II: Patients receive unmanipulated T cell-replete BM on day 0.

      GVHD PROPHYLAXIS: All patients receive tacrolimus IV on days -1 to +50 followed by a taper in
      the absence of grade II-IV aGVHD. Patients also receive methotrexate IV on days +1, +3, +6,
      and +11.

      After completion of study treatment, patients are followed up periodically.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility achievement
time frame: Up to 2 years
description: Success defined as achievement of cell selection goals for two consecutive Naive T cells (TN)-depleted peripheral blood stem cells (PBSC) hematopoietic cell transplantation (HCTs) at each study site (Feasibility)
measure: Engraftment of neutrophils by day 28 (Feasibility)
time frame: At day 28
description: Success defined as achievement neutrophil engraftment (absolute neutrophil count [ANC] >= 500/mm^3) on first day of three consecutive laboratory values obtained on different days.
measure: Current-graft versus host disease (GVHD)-free, relapse-free survival (Randomized Controlled Trial [RCT])
time frame: At 1 year
description: Defined as alive, no relapse after HCT, no current GVHD requiring prednisone, no graft rejection or graft failure. The proportion of subjects meeting the primary endpoint will be described in each arm with 90% confidence intervals (CI) and compared between arms using the chi-square test. A two-sided 10% significance level will be used for this comparison.
measure: Chronic GVHD (cGVHD) meeting National Institutes of Health (NIH) criteria and requiring prednisone (RCT)
time frame: At 1 and 2 years
description: Cumulative incidence curve will be computed for each arm along with a 90% CI at 1 year and 2 years post-HCT. Death and/or relapse prior to occurrence of cGVHD will be considered as competing risks. The cumulative incidence curves will be compared between arms using Gray's test. The maximum severity of cGVHD will also be described in each arm and compared using the chi-squared test.
measure: Proportion of subjects alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD (RCT)
time frame: At 3, 6, 9, 12, 15, 18, 21 and 24 months post HCT
description: Proportions of subjects alive without requiring use of prednisone (or equivalent systemic corticosteroid) for GVHD will be estimated with 90% CI for both arms at time points over 24 months, and compared using the chi-squared test.
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group type: Experimental
description: CONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.
CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2.
CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1.
TRANSPLANT: Patients receive naive T-cell depleted PBSCs on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11.
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
arm group type: Active Comparator
description: CONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.
CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2.
CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1.
TRANSPLANT: Patients receive unmanipulated T cell-replete BM on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11.
intervention type: Radiation
intervention name: Total-Body Irradiation
description: Undergo TBI
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: Total Body Irradiation
other name: Whole-Body Irradiation
other name: SCT_TBI
other name: TBI
other name: Whole Body Irradiation
intervention type: Drug
intervention name: Thiotepa
description: Given IV
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: 1,1',1"-phosphinothioylidynetrisaziridine
other name: Oncotiotepa
other name: STEPA
other name: Tepadina
other name: Tespamin
other name: Tespamine
other name: Thio-Tepa
other name: Thiofosfamide
other name: Thiofozil
other name: Thiophosphamide
other name: Thiophosphoramide
other name: triethylenethiophosphoramide
intervention type: Drug
intervention name: Fludarabine
description: Given IV
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: 2-Fluoro-9-beta-arabinofuranosyladenine
other name: 2-Fluorovidarabine
other name: Fluradosa
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: Cycloblastin
other name: Cytophosphane
intervention type: Drug
intervention name: Busulfan
description: Given IV
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: Bussulfam
other name: Busulfanum
other name: Busulfex
other name: Busulphan
other name: Misulban
other name: Misulfan
other name: Mitosan
other name: Myeleukon
intervention type: Procedure
intervention name: Allogeneic Bone Marrow Transplantation
description: Receive unmanipulated T cell replete BM
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: Allo BMT
other name: Allogeneic Blood and Marrow Transplantation
other name: Allogeneic BMT
intervention type: Drug
intervention name: Tacrolimus
description: Given IV
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: Fujimycin
other name: Hecoria
other name: Prograf
other name: Protopic
intervention type: Drug
intervention name: Methotrexate
description: Given IV
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
arm group label: Arm II (chemotherapy, unmanipulated T cell replete BM)
other name: Abitrexate
other name: Alpha-Methopterin
other name: Amethopterin
other name: Brimexate
other name: Emtexate
other name: Emthexat
other name: Emthexate
other name: Farmitrexat
other name: Medsatrexate
other name: Methoblastin
other name: Rheumatrex
intervention type: Procedure
intervention name: Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation
description: Receive naive T-cell depleted PBSCs
arm group label: Arm I (chemotherapy, naive T-cell depleted PBSC)
criteria: 
gender: All
minimum age: 6 Months
maximum age: 22 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marie Bleakley
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Marie Bleakley
phone: 206-667-6572
email: mbleakle@fredhutch.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Preleukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Biphenotypic, Acute
mesh term: Bronchiolitis Obliterans Syndrome
mesh term: Myelodysplastic Syndromes
mesh term: Anemia, Refractory, with Excess of Blasts
mesh term: Graft vs Host Disease
mesh term: Syndrome
mesh term: Acute Disease
mesh term: Vidarabine
mesh term: Cyclophosphamide
mesh term: Busulfan
mesh term: Thiotepa
mesh term: Methotrexate
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Tacrolimus
sharing ipd: No