<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/NCT03263559</url>
  </required_header>
  <id_info>
    <org_study_id>BMTCTN1507</org_study_id>
    <secondary_id>2U10HL069294-11</secondary_id>
    <secondary_id>5U24CA076518</secondary_id>
    <nct_id>NCT03263559</nct_id>
  </id_info>
  <brief_title>Haploidentical Bone Marrow Transplantation in Sickle Cell Patients (BMTCTN1507)</brief_title>
  <official_title>Reduced Intensity Conditioning for Haploidentical Bone Marrow Transplantation in Patients With Symptomatic Sickle Cell Disease. (BMTCTN1507)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Blood and Marrow Transplant Clinical Trials Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Marrow Donor Program</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical College of Wisconsin</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase II, single arm, multi-center trial, designed to estimate the efficacy and&#xD;
      toxicity of haploidentical bone marrow transplantation (BMT) in patients with sickle cell&#xD;
      disease (SCD). Based on their age and entry criteria patients are stratified into two groups:&#xD;
      (1) children with severe SCD; and (2) adults with severe SCD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed as a Phase II multi-center trial to determine the feasibility of&#xD;
      achieving a high rate of event-free survival (EFS) at 2 years post transplant using&#xD;
      pre-conditioning hydroxyurea (HU) with a conditioning regimen that consists of a combination&#xD;
      of Thymoglobulin/Cyclophosphamide/Fludarabine/Thiotepa with post-grafting high-dose&#xD;
      cyclophosphamide in patients with severe SCD who have HLA-haploidentical donors. EFS is&#xD;
      defined as survival without a qualifying event. This is a single arm study in which&#xD;
      participants will be enrolled into one of two strata. The first stratum will be restricted to&#xD;
      children who have stroke and 40 children will be enrolled in this stratum. The second stratum&#xD;
      will consist of adult patients with severe sickle cell disease and 40 participants will be&#xD;
      enrolled in this stratum.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 3, 2017</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Two-Year Post-Transplant Event Free Survival (EFS)</measure>
    <time_frame>2 years</time_frame>
    <description>EFS is defined as survival without a qualifying event. Primary graft rejection, secondary graft rejection, second infusion of hematopoietic cells or death will count as events for this endpoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1 and 2 years</time_frame>
    <description>Death from any cause will be the event and patients will be censored at the date of last contact or two years post-transplant whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>One-Year Post-Transplant EFS</measure>
    <time_frame>1 year</time_frame>
    <description>EFS is defined as survival without a qualifying event, Primary graft rejection, secondary graft rejection, second infusion of hematopoietic cells or death will count as events for this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft Rejection</measure>
    <time_frame>Day 42</time_frame>
    <description>Graft rejection is defined as not having engraftment on or before Day 42 post-transplant. Engraftment is defined as having greater than or equal to 5% donor cells post-transplant, from any molecular chimerism assessment (e.g., unsorted, myeloid, or T-cell) on a peripheral blood or bone marrow aspirate sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chimerism</measure>
    <time_frame>Days 28, 100, and 180 and at 1 and 2 years</time_frame>
    <description>Characterize donor hematopoietic chimerism in peripheral blood will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Recurrence</measure>
    <time_frame>2 years</time_frame>
    <description>Disease recurrence is defined as the return of sickle erythropoiesis (in the absence of red blood count transfusion, Hb S level &gt; 70%), or primary or secondary graft rejection, as defined above, or second infusion of hematopoietic cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Quality of Life (QoL)</measure>
    <time_frame>1 and 2 years</time_frame>
    <description>Health-Related QoL will be measured using patient reported surveys.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A conditioning regimen with Hydroxyurea, rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide, Total Body Irradiation, and Mesna will be administered prior to Haploidentical Bone Marrow Transplantation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Haploidentical Bone Marrow Transplantation</intervention_name>
    <description>Eligible patients with a first degree Human Leukocyte Antigen (HLA)- haploidentical donor will undergo Haploidentical bone marrow transplantation at Day 0 with non T-cell depleted bone marrow. For Graft-vs-Host Disease (GVHD) prophylaxis, patients will be given sirolimus and mycophenolate mofetil beginning on Day +5.</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxyurea</intervention_name>
    <description>HU will be given daily at 30mg/kg from Day -70 through Day -10.</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>Hydrea</other_name>
    <other_name>Droxia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rabbit-ATG</intervention_name>
    <description>Rabbit-ATG (rATG) will be given at 0.5mg/kg on Day -9, and at 2.0mg/kg on Day -8 and Day -7.</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>Thymoglobulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thiotepa</intervention_name>
    <description>Thiotepa will be given at 10mg/kg on Day -7</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>Chemo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine</intervention_name>
    <description>Fludarabine will be given at 30mg/m2 from Day -6 to Day -2</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>Fludara</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide will be given at 14.5mg/kg on Day -6 and Day -5, and at 50 mg/kg on Days +3 and +4.</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>Cytoxan®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Total Body Irradiation</intervention_name>
    <description>Total Body Irradiation will be given at 200cGy on Day -1</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>TBI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesna</intervention_name>
    <description>Mesna will be given at 40mg/kg on Days +3 and +4</description>
    <arm_group_label>Haploidentical Transplantation</arm_group_label>
    <other_name>Mesnex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Adequate physical function as measured by all of the following:&#xD;
&#xD;
          1. A Karnofsky/Lansky performance score of ≥ 60.&#xD;
&#xD;
          2. Cardiac function: Left ventricular ejection fraction (LVEF) &gt; 40%; or LV shortening&#xD;
             fraction &gt; 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA)&#xD;
             scan.&#xD;
&#xD;
          3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥ 85% and&#xD;
             Diffusing capacity of the lung for carbon monoxide (DLCO) &gt; 40% (corrected for&#xD;
             hemoglobin).&#xD;
&#xD;
          4. Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated&#xD;
             or measured creatinine clearance ≥ 70 mL/min/1.73 m²&#xD;
&#xD;
          5. Hepatic function:&#xD;
&#xD;
               1. Serum conjugated (direct) bilirubin &lt; 2x upper limit of normal for age as per&#xD;
                  local laboratory. Participants with hyperbilirubinemia as the result of&#xD;
                  hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not&#xD;
                  excluded.&#xD;
&#xD;
               2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) &lt; 5x upper&#xD;
                  limit of normal as per local laboratory.&#xD;
&#xD;
          6. Liver MRI using a validated methodology per institutional preference (T2* or R2* or by&#xD;
             ferriscan [R2 MRI]) for estimation of hepatic iron content is required for&#xD;
             participants who are currently receiving ≥8 packed red blood cell transfusions per&#xD;
             year for ≥1 year or have received ≥20 packed red blood cell transfusions (lifetime&#xD;
             cumulative). Participants who have hepatic iron content ≥ 10 mg Fe/g liver dry weight&#xD;
             by liver MRI must have a Gastroenterology/hepatology consultation with liver biopsy&#xD;
             and histological examination including documentation of the absence of cirrhosis,&#xD;
             bridging fibrosis, and active hepatitis.&#xD;
&#xD;
          7. Participants must be HLA typed at high resolution using DNA based typing at HLA-A, -B,&#xD;
             -C, DRB1, and have available:&#xD;
&#xD;
             An HLA haploidentical first degree relative donor (parents, siblings or half siblings,&#xD;
             or children) with 2, 3, or 4 (out of 8) HLA-mismatches who is willing and able to&#xD;
             donate bone marrow. A unidirectional mismatch in either the graft versus host or host&#xD;
             versus graft direction is considered a mismatch. The donor and recipient must be HLA&#xD;
             identical for at least one antigen (using high resolution DNA based typing) at the&#xD;
             following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this&#xD;
             criterion shall be considered sufficient evidence that the donor and recipient share&#xD;
             one HLA haplotype, and typing of additional family members is not required.&#xD;
             Confirmatory donor HLA typing must be completed &lt; 100 days prior to Segment A&#xD;
             enrollment&#xD;
&#xD;
          8. Umbilical cord blood or peripheral blood stem cell donors will not be accepted.&#xD;
&#xD;
        Inclusion Criteria for Stratum 1: Children Ages 5.00 - 14.99 years of age at enrollment&#xD;
&#xD;
          1. Age 5.00 - 14.99 years at Segment A enrollment&#xD;
&#xD;
          2. Participants with sickle cell anemiam disease (Hb SS or Sß° Thalassemia) who have one&#xD;
             or more of the following:&#xD;
&#xD;
               1. A neurological event resulting in focal neurologic deficits that lasted ≥ 24&#xD;
                  hours (classical clinical definition of stroke, not requiring imaging studies of&#xD;
                  the brain) OR a focal neurological event resulting in abnormalities on&#xD;
                  T2-weighted or FLAIR images using a MRI scan, indicative of an acute infarct,&#xD;
                  with no other reasonable medical explanation (definition of a stroke supported&#xD;
                  with MRI imaging scans of the brain), OR both.&#xD;
&#xD;
               2. Abnormal transcranial Doppler (TCD) measurement with a timed average maximum mean&#xD;
                  velocity of at least 200 cm/sec in the terminal portion of the internal carotid&#xD;
                  or proximal portion of middle cerebral artery or if the imaging TCD method is&#xD;
                  used &gt; 185 cm/sec plus evidence of intracranial vasculopathy.&#xD;
&#xD;
               3. Silent Cerebral Infarct defined as an infarct-like lesion based on an MRI signal&#xD;
                  abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or&#xD;
                  T2-weighted images (or similar image with 3D imaging) and documented neurological&#xD;
                  examination performed by a neurologist demonstrating the participant has a normal&#xD;
                  neurologic examination or an abnormality on examination that could not be&#xD;
                  explained by the location of the brain lesion(s).&#xD;
&#xD;
               4. Acute severe vaso-occlusive pain episodes requiring hospitalization and&#xD;
                  recalcitrant to maximum medical therapy. Episodes of pain to be adjudicated by&#xD;
                  selected committee.&#xD;
&#xD;
               5. One acute chest syndrome episode resulting in intensive care admission requiring&#xD;
                  non-mechanical ventilatory support: simple nasal cannula, face mask that requires&#xD;
                  oxygen content (venti mask, non-rebreather), simple nasal cannula, face mask&#xD;
                  O2(e.g. ventimask, rebreather), CPAP, SiPAP, BiPAP, high flow nasal cannula&#xD;
                  (HFNC) or invasive mechanical ventilatory support (delivered by ETT or trach).&#xD;
&#xD;
               6. Right heart catheterization confirmed pulmonary artery pressure &gt;25 mmHG or mean&#xD;
                  pulmonary vascular resistance 206(57-421) dyn·s·cm-5&#xD;
&#xD;
               7. Essential hypertension on antihypertensive medications &gt;95% upper limit of normal&#xD;
                  age (as defined according to the American Academy of Pediatrics)&#xD;
&#xD;
               8. Recurrent priapism (episodes lasting at least 4 hours at least twice in the last&#xD;
                  12 months or 3 times in the last 24 months) recalcitrant to medical treatment or&#xD;
                  unable to use hydroxyurea due to SCD phenotype with the approval of the&#xD;
                  adjudication committee&#xD;
&#xD;
        Inclusion Criteria for Stratum 2: Adults Ages 15.00 - 45.99 at enrollment&#xD;
&#xD;
        Participants with sickle cell anemia (Hb SS or Sß° Thalassemia) who are 15.00 - 45.99 years&#xD;
        of age at enrollment AND who have one or more of the following:&#xD;
&#xD;
          1. Age 15.00 - 45.99 years at Segment A enrollment&#xD;
&#xD;
          2. Participants with sickle cell anemia (Hb SS or Sß° Thalassemia) who have one or more&#xD;
             of the following:&#xD;
&#xD;
               1. A neurological event resulting in focal neurologic deficits that lasted ≥ 24&#xD;
                  hours (classical clinical definition of stroke, not requiring imaging studies of&#xD;
                  the brain) OR a focal neurological event resulting in abnormalities on&#xD;
                  T2-weighted or FLAIR images using a MRI scan, indicative of an acute infarct,&#xD;
                  with no other reasonable medical explanation (definition of a stroke supported&#xD;
                  with MRI imaging scans of the brain), OR both.&#xD;
&#xD;
               2. History of two or more episodes of acute chest syndrome (ACS) in the 2-year&#xD;
                  period preceding enrollment despite the institution of supportive care measures&#xD;
                  (i.e. asthma therapy and/or hydroxyurea);&#xD;
&#xD;
               3. History of three or more severe vaso-occlusive pain crises per year in the 2-year&#xD;
                  period preceding enrollment despite the institution of supportive care measures&#xD;
                  (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes&#xD;
                  related to priapism, osteonecrosis or any sickle-related complication are&#xD;
                  acceptable;&#xD;
&#xD;
               4. Administration of regular RBC transfusion therapy, defined as receiving ≥8 packed&#xD;
                  red blood cell transfusions per year for ≥1 year in the 12 months before&#xD;
                  enrollment to prevent vaso-occlusive clinical complications (i.e. pain, stroke,&#xD;
                  and acute chest syndrome);&#xD;
&#xD;
               5. An echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥&#xD;
                  2.7 m/sec.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants who have an HLA-matched sibling who is able and willing to donate bone&#xD;
             marrow. Patients with a HLA-matched unrelated donor are not excluded.&#xD;
&#xD;
          2. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment&#xD;
             (currently taking medication with evidence of progression of clinical symptoms or&#xD;
             radiologic findings).&#xD;
&#xD;
          3. Evidence of HIV infection or known HIV positive serology.&#xD;
&#xD;
          4. Participants who have received a previous hematopoetic cell transplant (HCT).&#xD;
&#xD;
          5. Participants who have had an Encephaloduroarteriosynangiosis (EDAS) procedure in the 6&#xD;
             months prior to enrollment&#xD;
&#xD;
          6. Participants who have received a prior solid organ transplant&#xD;
&#xD;
          7. Participants who have participated in another clinical trial in which the patient&#xD;
             received an investigational or off-label use of a drug or device within 3 months of&#xD;
             enrollment.&#xD;
&#xD;
          8. Females who are pregnant or breastfeeding.&#xD;
&#xD;
          9. Participants with clinically significant, uncontrolled autoimmune disease, requiring&#xD;
             active medical management (immunosuppressive therapy or chemotherapy), which, in the&#xD;
             judgment of the local Principal Investigator, indicates that the patient could not&#xD;
             tolerate transplantation.&#xD;
&#xD;
         10. Females of child bearing potential (to include all female participants &gt; 10 years of&#xD;
             age, unless postmenopausal for a minimum of 1 year before the time of consent or&#xD;
             surgically sterilized), who do not agree to practice two (2) effective methods of&#xD;
             contraception at the same time, or do not agree to practice true abstinence when this&#xD;
             is in line with the preferred and usual lifestyle of the subject, from the time of&#xD;
             signing of informed consent through 12 months post-transplant.&#xD;
&#xD;
         11. Males (even if surgical sterilized) who do not agree to practice effective barrier&#xD;
             contraception, or who do not agree to practice true abstinence from the time of&#xD;
             signing informed consent through 12 months post-transplant.&#xD;
&#xD;
         12. Presence of anti-donor specific HLA antibodies. HLA antibody presence and specificity&#xD;
             will be determined by solid phase immunoassays. An anti-donor specific HLA antibody&#xD;
             will be considered positive when the mean fluorescence intensity (MFI) is higher than&#xD;
             the cut-off defined by each institution. Recommended cut-off values are MFI &gt;1000 for&#xD;
             donor specific antibody to HLA-A, -B, and DRB1 and MFI &gt;2000 for HLA-C, DQB1 and DPB1.&#xD;
             This must be measured before the final donor selection, and &lt; 100 days before&#xD;
             enrollment in Segment A (preferably &lt; 30 days before Segment A enrollment). If MFI&#xD;
             &gt;1000 for donor specific antibody to HLA-A, -B, DRB1 and/or MFI &gt;2000 for HLA-C, DQB1&#xD;
             and DPB1, documentation must be submitted to the DCC coordinator for review and&#xD;
             approval by a Protocol Chair and/or Protocol Officer prior to enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mary Horowitz, MD</last_name>
    <role>Study Director</role>
    <affiliation>Center for International Blood and Marrow Transplant Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado - Denver/Children's Hospital of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nicklaus Children's Hospital/University of Miami Children's Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northside Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Children's Hospital at IU Health</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Medical Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Michigan</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helen Devos Children's at Spectrum Health</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardinal Glennon Children's Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University, St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Center</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Health/Monter Cancer Center</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Children's Hospital</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Cleveland/Case Western</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205-2696</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Healthcare/West Cancer Center</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital (Baylor)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas/MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Transplant Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Medical College of Wisconsin</name>
      <address>
        <city>Wauwatosa</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bmtctn.net/</url>
    <description>Blood and Marrow Transplant Clinical Trials Network Website</description>
  </link>
  <link>
    <url>https://bethematch.org/</url>
    <description>National Marrow Donor Program</description>
  </link>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Reduced Intensity Conditioning</keyword>
  <keyword>Haploidentical</keyword>
  <keyword>Bone Marrow</keyword>
  <keyword>Transplant</keyword>
  <keyword>Sickle Cell Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Thiotepa</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Hydroxyurea</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Within 6 months of official study closure at participating sites.</ipd_time_frame>
    <ipd_access_criteria>Available to the public</ipd_access_criteria>
    <ipd_url>https://biolincc.nhlbi.nih.gov/home/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 19, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT03263559/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03263559
org study id: BMTCTN1507
secondary id: 2U10HL069294-11
secondary id: 5U24CA076518
nct id: NCT03263559
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a Phase II, single arm, multi-center trial, designed to estimate the efficacy and
      toxicity of haploidentical bone marrow transplantation (BMT) in patients with sickle cell
      disease (SCD). Based on their age and entry criteria patients are stratified into two groups:
      (1) children with severe SCD; and (2) adults with severe SCD.
This study is designed as a Phase II multi-center trial to determine the feasibility of
      achieving a high rate of event-free survival (EFS) at 2 years post transplant using
      pre-conditioning hydroxyurea (HU) with a conditioning regimen that consists of a combination
      of Thymoglobulin/Cyclophosphamide/Fludarabine/Thiotepa with post-grafting high-dose
      cyclophosphamide in patients with severe SCD who have HLA-haploidentical donors. EFS is
      defined as survival without a qualifying event. This is a single arm study in which
      participants will be enrolled into one of two strata. The first stratum will be restricted to
      children who have stroke and 40 children will be enrolled in this stratum. The second stratum
      will consist of adult patients with severe sickle cell disease and 40 participants will be
      enrolled in this stratum.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Two-Year Post-Transplant Event Free Survival (EFS)
time frame: 2 years
description: EFS is defined as survival without a qualifying event. Primary graft rejection, secondary graft rejection, second infusion of hematopoietic cells or death will count as events for this endpoint.
measure: Overall Survival
time frame: 1 and 2 years
description: Death from any cause will be the event and patients will be censored at the date of last contact or two years post-transplant whichever comes first.
measure: One-Year Post-Transplant EFS
time frame: 1 year
description: EFS is defined as survival without a qualifying event, Primary graft rejection, secondary graft rejection, second infusion of hematopoietic cells or death will count as events for this endpoint.
measure: Graft Rejection
time frame: Day 42
description: Graft rejection is defined as not having engraftment on or before Day 42 post-transplant. Engraftment is defined as having greater than or equal to 5% donor cells post-transplant, from any molecular chimerism assessment (e.g., unsorted, myeloid, or T-cell) on a peripheral blood or bone marrow aspirate sample.
measure: Chimerism
time frame: Days 28, 100, and 180 and at 1 and 2 years
description: Characterize donor hematopoietic chimerism in peripheral blood will be assessed.
measure: Disease Recurrence
time frame: 2 years
description: Disease recurrence is defined as the return of sickle erythropoiesis (in the absence of red blood count transfusion, Hb S level > 70%), or primary or secondary graft rejection, as defined above, or second infusion of hematopoietic cells.
measure: Patient Reported Quality of Life (QoL)
time frame: 1 and 2 years
description: Health-Related QoL will be measured using patient reported surveys.
arm group label: Haploidentical Transplantation
arm group type: Experimental
description: A conditioning regimen with Hydroxyurea, rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide, Total Body Irradiation, and Mesna will be administered prior to Haploidentical Bone Marrow Transplantation.
intervention type: Procedure
intervention name: Haploidentical Bone Marrow Transplantation
description: Eligible patients with a first degree Human Leukocyte Antigen (HLA)- haploidentical donor will undergo Haploidentical bone marrow transplantation at Day 0 with non T-cell depleted bone marrow. For Graft-vs-Host Disease (GVHD) prophylaxis, patients will be given sirolimus and mycophenolate mofetil beginning on Day +5.
arm group label: Haploidentical Transplantation
intervention type: Drug
intervention name: Hydroxyurea
description: HU will be given daily at 30mg/kg from Day -70 through Day -10.
arm group label: Haploidentical Transplantation
other name: Hydrea
other name: Droxia
intervention type: Drug
intervention name: Rabbit-ATG
description: Rabbit-ATG (rATG) will be given at 0.5mg/kg on Day -9, and at 2.0mg/kg on Day -8 and Day -7.
arm group label: Haploidentical Transplantation
other name: Thymoglobulin
intervention type: Drug
intervention name: Thiotepa
description: Thiotepa will be given at 10mg/kg on Day -7
arm group label: Haploidentical Transplantation
other name: Chemo
intervention type: Drug
intervention name: Fludarabine
description: Fludarabine will be given at 30mg/m2 from Day -6 to Day -2
arm group label: Haploidentical Transplantation
other name: Fludara
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide will be given at 14.5mg/kg on Day -6 and Day -5, and at 50 mg/kg on Days +3 and +4.
arm group label: Haploidentical Transplantation
other name: Cytoxan®
intervention type: Radiation
intervention name: Total Body Irradiation
description: Total Body Irradiation will be given at 200cGy on Day -1
arm group label: Haploidentical Transplantation
other name: TBI
intervention type: Drug
intervention name: Mesna
description: Mesna will be given at 40mg/kg on Days +3 and +4
arm group label: Haploidentical Transplantation
other name: Mesnex
criteria: 
gender: All
minimum age: 5 Years
maximum age: 45 Years
healthy volunteers: No
last name: Mary Horowitz, MD
role: Study Director
affiliation: Center for International Blood and Marrow Transplant Research
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.bmtctn.net/
description: Blood and Marrow Transplant Clinical Trials Network Website
url: https://bethematch.org/
description: National Marrow Donor Program
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Cyclophosphamide
mesh term: Thiotepa
mesh term: Fludarabine
mesh term: Hydroxyurea
mesh term: Thymoglobulin
sharing ipd: Yes
ipd description: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: Within 6 months of official study closure at participating sites.
ipd access criteria: Available to the public
ipd url: https://biolincc.nhlbi.nih.gov/home/
provided document: 