<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/NCT03249831</url>
  </required_header>
  <id_info>
    <org_study_id>16453</org_study_id>
    <nct_id>NCT03249831</nct_id>
  </id_info>
  <brief_title>A Blood Stem Cell Transplant for Sickle Cell Disease</brief_title>
  <official_title>Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Sickle Cell Disease Patients With COH-MC-17: a Non-Myeloablative, Conditioning Regimen and CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>California Institute for Regenerative Medicine (CIRM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical 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>
      Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the&#xD;
      immune system (which fight infections) and platelets (which help the blood clot).&#xD;
&#xD;
      Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell&#xD;
      transplant from a donor is a treatment option for patients with severe sickle cell disease.&#xD;
      The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will&#xD;
      be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then&#xD;
      make normal red blood cells - as well as other types of blood cells - in the patient. When&#xD;
      blood cells from two people co-exist in the patient, this is called mixed chimerism.&#xD;
&#xD;
      Most children are successfully treated with blood stem cells from a sibling (brother/sister)&#xD;
      who completely shares their tissue type (full-matched donor). However, transplant is not an&#xD;
      option for patients who (1) have serious medical problems, and/or (2) do not have a&#xD;
      full-matched donor. Most patients will have a relative who shares half of their tissue type&#xD;
      (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical&#xD;
      donor).&#xD;
&#xD;
      Adult patients with severe sickle cell disease were successfully treated with a half-matched&#xD;
      transplant in a clinical study. Researchers would like to make half-matched transplant an&#xD;
      option for more patients by (1) improving transplant success and (2) reducing&#xD;
      transplanted-related complications.&#xD;
&#xD;
      This research transplant is being tested in this Pilot study for the first time. It is&#xD;
      different from a standard transplant because:&#xD;
&#xD;
        1. Half-matched related donors will be used, and&#xD;
&#xD;
        2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone&#xD;
           marrow cells (non-myeloablative treatment) will be used to prepare the patient for&#xD;
           transplant, and&#xD;
&#xD;
        3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted)&#xD;
           before giving the blood stem cell transplant to the patient to improve transplant&#xD;
           outcomes.&#xD;
&#xD;
      It is hoped that the research transplant:&#xD;
&#xD;
        1. Will reverse sickle cell disease and improve patient quality of life,&#xD;
&#xD;
        2. Will reduce side effects and help the patient recover faster from the transplant,&#xD;
&#xD;
        3. Help the patient keep the transplant longer and&#xD;
&#xD;
        4. Reduce serious transplant-related complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot study to determine the safety and feasibility of the COH-MC-17 regimen and&#xD;
      ability of the regimen to induce a mixed chimeric status in severe sickle cell disease&#xD;
      patients (hemoglobin SS or S-βº Thalassemia). The COH-MC-17 regimen consists of a&#xD;
      non-myeloablative regimen (cyclophosphamide, pentostatin and rabbit-anti-thymocyte globulin&#xD;
      (ATG)) followed by a CD4+ T-cell-depleted haploidentical hematopoietic cell transplant&#xD;
      (HaploHCT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 4, 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 1</phase>
  <study_type>Interventional</study_type>
  <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>Toxicity per NCI-Common Terminology Criteria for Adverse Events version 4.0</measure>
    <time_frame>Day -22 to 2 years post-transplant</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Unacceptable Toxicity at least possibly related to COH-MC-17</measure>
    <time_frame>Day -22 to Day +60 post-transplant</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mixed Chimerism defined as 30-90% donor cells</measure>
    <time_frame>Day +60 post-transplant</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product</measure>
    <time_frame>From apheresis to Day 0</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events of Grade 3 or higher</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutrophil count ≥ 500/mm3, time to recovery</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet count ≥ 20,000/mm3, time to recovery</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Marrow failure</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sickle cell disease related complications</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Graft versus Host Disease per 1994 Keystone Consensus Criteria</measure>
    <time_frame>Day + 100 post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chronic Graft versus Host Disease per 2014 National Institutes of Health Consensus Criteria</measure>
    <time_frame>Day+ 180, + 1 year and +2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-Free Survival</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-Free Survival</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Relapse</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent post-immunosuppressant mixed chimerism</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
    <description>Between 5% and 95% donor chimerism at two years post- transplant, at least 6 months post- immunosuppressant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent immunosuppressant -dependent mixed chimerism</measure>
    <time_frame>+2 years post-transplant</time_frame>
    <description>Between 5% and 95% donor chimerism at two years post- transplant and on immunosuppressant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete chimerism: &gt;95% donor chimerism</measure>
    <time_frame>+2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary donor graft failure: Defined as &lt; 5% donor chimerism by Day + 30 post- transplant</measure>
    <time_frame>Day +30 post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary donor graft failure: Defined as &lt; 5% donor chimerism beyond Day +30 in patients with prior documentation of ≥ 5% donor cells by Day +30</measure>
    <time_frame>&gt; Day + 30 up to 2 years post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Donor chimerism in blood</measure>
    <time_frame>Day +30, Day +60, Day +100, Day+180, and +1 yr, +1.5 yr, +2yr post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Donor chimerism in bone marrow</measure>
    <time_frame>Day + 100, Day + 180 and + 1 yr post-transplant</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent HbS levels</measure>
    <time_frame>Baseline, and then Day + 30, Day + 100, Day + 180, +1 yr, +1.5, +2yr post-transplant</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Ratio donor: recipient de novo thymic T cells</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Ratio donor: recipient FoxP3+ regulatory T cells</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Tolerance status of donor: recipient type T cells</measure>
    <time_frame>Up to 2 years post-transplant</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Sickle Cell Disease</condition>
  <condition>Sickle Cell Disorder</condition>
  <condition>Hemoglobinopathies</condition>
  <condition>Thalassemia</condition>
  <condition>Anemia, Sickle Cell</condition>
  <arm_group>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0.&#xD;
Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant.&#xD;
The minimally manipulated transplant product is manufactured using the CliniMACS device.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Orally daily</description>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pentostatin</intervention_name>
    <description>Intravenous</description>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <other_name>NIPENT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rabbit anti-thymocyte globulin</intervention_name>
    <description>Intravenous</description>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <other_name>Rabbit ATG</other_name>
    <other_name>Thymoglobulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Initially IV. If patient tolerates, convert to oral.</description>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <other_name>PROGRAF®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil</intervention_name>
    <description>IV or oral</description>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <other_name>MMF</other_name>
    <other_name>CellCept®</other_name>
    <other_name>Myfortic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant</intervention_name>
    <description>Infusion</description>
    <arm_group_label>COH-MC-17 and immunosuppressants</arm_group_label>
    <other_name>CD4+ T-cell depleted HaploHCT</other_name>
    <other_name>CD4+ T-cell depleted hematopoietic progenitor cell (HPC) product</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion:&#xD;
&#xD;
          1. Confirmed diagnosis of hemoglobin SS or S-βº Thalassemia sickle cell disease&#xD;
&#xD;
          2. Severe disease status as defined by presence of one or more of the following:&#xD;
&#xD;
               1. Clinically significant neurologic event (stroke) or any neurological deficit&#xD;
                  lasting &gt; 24 hours; or increased transcranial Doppler velocity (&gt;200 m/s). A&#xD;
                  stroke is defined as a sudden neurologic change lasting more than 24 hours that&#xD;
                  is accompanied by cerebral magnetic resonance imaging (MRI) changes.&#xD;
&#xD;
               2. History of ≥ 1 episodes of acute chest syndrome (ACS) in the 2-year period&#xD;
                  preceding enrollment despite the institution of supportive care measures (i.e.&#xD;
                  asthma therapy and/or hydroxyurea).&#xD;
&#xD;
               3. History of ≥ 2 severe vaso-occlusive pain crises (VOC) 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). A severe VOC is&#xD;
                  defined as an episode of pain lasting more than 2 hours severe enough to require&#xD;
                  care at a medical facility. Note that priapism that lasts more than 2 hours and&#xD;
                  requires care at a medical facility is also considered a VOC.&#xD;
&#xD;
               4. Osteonecrosis of ≥ 2 joints despite the institution of supportive care measures.&#xD;
&#xD;
               5. Prior treatment with regular RBC transfusion therapy, defined as receiving ≥ 8&#xD;
                  transfusions per year for &gt; 1 year to prevent vaso-occlusive clinical&#xD;
                  complications (i.e. pain, stroke, and acute chest syndrome)&#xD;
&#xD;
          3. No HLA matched sibling or 10/10 matched unrelated donor&#xD;
&#xD;
          4. Related donor who:&#xD;
&#xD;
               1. Is genotypically haploidentical on HLA-A, B, C and DRB1 loci AND&#xD;
&#xD;
               2. Meets institutional criteria&#xD;
&#xD;
          5. Failed prior hydroxyurea therapy or have intolerance to hydroxyurea&#xD;
&#xD;
          6. Meets protocol specified organ function criteria&#xD;
&#xD;
          7. Women of childbearing potential or sexually active male: Agreement to use adequate&#xD;
             contraception prior to study entry and 6 months post-transplant.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Prior stem cell transplant&#xD;
&#xD;
          2. Prior bone marrow transplant&#xD;
&#xD;
          3. Concurrent other investigational agents, chemotherapy, biological therapy or radiation&#xD;
             therapy&#xD;
&#xD;
          4. Planned use of moderate and strong CYP3A4 inhibitors&#xD;
&#xD;
          5. Active infection&#xD;
&#xD;
          6. Major surgery within the last 30 days&#xD;
&#xD;
          7. Clinically significant liver fibrosis or cirrhosis if on chronic transfusion therapy &gt;&#xD;
             6 months&#xD;
&#xD;
          8. Active malignancy (other than non-melanoma skin cancers)&#xD;
&#xD;
          9. History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to any in the pre- or post-transplant regimen.&#xD;
&#xD;
         10. Women of childbearing potential: pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph Rosenthal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Sickle Cell Disorders</keyword>
  <keyword>Hemoglobinopathies</keyword>
  <keyword>Thalassemia</keyword>
  <keyword>Anemia, Sickle Cell</keyword>
  <keyword>Haploidentical Transplant</keyword>
  <keyword>Nonmyeloablative Conditioning</keyword>
  <keyword>CD4+ T cell</keyword>
  <keyword>CD4+ T cell-depleted Hematopoietic Cell Transplant</keyword>
  <keyword>Mixed Chimerism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>Hemoglobinopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Pentostatin</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
    <mesh_term>Antilymphocyte Serum</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03249831
org study id: 16453
nct id: NCT03249831
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the
      immune system (which fight infections) and platelets (which help the blood clot).

      Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell
      transplant from a donor is a treatment option for patients with severe sickle cell disease.
      The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will
      be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then
      make normal red blood cells - as well as other types of blood cells - in the patient. When
      blood cells from two people co-exist in the patient, this is called mixed chimerism.

      Most children are successfully treated with blood stem cells from a sibling (brother/sister)
      who completely shares their tissue type (full-matched donor). However, transplant is not an
      option for patients who (1) have serious medical problems, and/or (2) do not have a
      full-matched donor. Most patients will have a relative who shares half of their tissue type
      (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical
      donor).

      Adult patients with severe sickle cell disease were successfully treated with a half-matched
      transplant in a clinical study. Researchers would like to make half-matched transplant an
      option for more patients by (1) improving transplant success and (2) reducing
      transplanted-related complications.

      This research transplant is being tested in this Pilot study for the first time. It is
      different from a standard transplant because:

        1. Half-matched related donors will be used, and

        2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone
           marrow cells (non-myeloablative treatment) will be used to prepare the patient for
           transplant, and

        3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted)
           before giving the blood stem cell transplant to the patient to improve transplant
           outcomes.

      It is hoped that the research transplant:

        1. Will reverse sickle cell disease and improve patient quality of life,

        2. Will reduce side effects and help the patient recover faster from the transplant,

        3. Help the patient keep the transplant longer and

        4. Reduce serious transplant-related complications.
This is a pilot study to determine the safety and feasibility of the COH-MC-17 regimen and
      ability of the regimen to induce a mixed chimeric status in severe sickle cell disease
      patients (hemoglobin SS or S-βº Thalassemia). The COH-MC-17 regimen consists of a
      non-myeloablative regimen (cyclophosphamide, pentostatin and rabbit-anti-thymocyte globulin
      (ATG)) followed by a CD4+ T-cell-depleted haploidentical hematopoietic cell transplant
      (HaploHCT).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity per NCI-Common Terminology Criteria for Adverse Events version 4.0
time frame: Day -22 to 2 years post-transplant
measure: Unacceptable Toxicity at least possibly related to COH-MC-17
time frame: Day -22 to Day +60 post-transplant
measure: Mixed Chimerism defined as 30-90% donor cells
time frame: Day +60 post-transplant
measure: Feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product
time frame: From apheresis to Day 0
measure: Adverse events of Grade 3 or higher
time frame: Up to 2 years post-transplant
measure: Neutrophil count ≥ 500/mm3, time to recovery
time frame: Up to 2 years post-transplant
measure: Platelet count ≥ 20,000/mm3, time to recovery
time frame: Up to 2 years post-transplant
measure: Marrow failure
time frame: Up to 2 years post-transplant
measure: Sickle cell disease related complications
time frame: Up to 2 years post-transplant
measure: Non-relapse mortality
time frame: Up to 2 years post-transplant
measure: Acute Graft versus Host Disease per 1994 Keystone Consensus Criteria
time frame: Day + 100 post-transplant
measure: Chronic Graft versus Host Disease per 2014 National Institutes of Health Consensus Criteria
time frame: Day+ 180, + 1 year and +2 years post-transplant
measure: Overall Survival
time frame: Up to 2 years post-transplant
measure: Disease-Free Survival
time frame: Up to 2 years post-transplant
measure: Event-Free Survival
time frame: Up to 2 years post-transplant
measure: Disease Relapse
time frame: Up to 2 years post-transplant
measure: Persistent post-immunosuppressant mixed chimerism
time frame: Up to 2 years post-transplant
description: Between 5% and 95% donor chimerism at two years post- transplant, at least 6 months post- immunosuppressant
measure: Persistent immunosuppressant -dependent mixed chimerism
time frame: +2 years post-transplant
description: Between 5% and 95% donor chimerism at two years post- transplant and on immunosuppressant
measure: Complete chimerism: >95% donor chimerism
time frame: +2 years post-transplant
measure: Primary donor graft failure: Defined as < 5% donor chimerism by Day + 30 post- transplant
time frame: Day +30 post-transplant
measure: Secondary donor graft failure: Defined as < 5% donor chimerism beyond Day +30 in patients with prior documentation of ≥ 5% donor cells by Day +30
time frame: > Day + 30 up to 2 years post-transplant
measure: Donor chimerism in blood
time frame: Day +30, Day +60, Day +100, Day+180, and +1 yr, +1.5 yr, +2yr post-transplant
measure: Donor chimerism in bone marrow
time frame: Day + 100, Day + 180 and + 1 yr post-transplant
measure: Percent HbS levels
time frame: Baseline, and then Day + 30, Day + 100, Day + 180, +1 yr, +1.5, +2yr post-transplant
measure: Ratio donor: recipient de novo thymic T cells
time frame: Up to 2 years post-transplant
measure: Ratio donor: recipient FoxP3+ regulatory T cells
time frame: Up to 2 years post-transplant
measure: Tolerance status of donor: recipient type T cells
time frame: Up to 2 years post-transplant
arm group label: COH-MC-17 and immunosuppressants
arm group type: Experimental
description: Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0.
Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant.
The minimally manipulated transplant product is manufactured using the CliniMACS device.
intervention type: Drug
intervention name: Cyclophosphamide
description: Orally daily
arm group label: COH-MC-17 and immunosuppressants
other name: Cytoxan
intervention type: Drug
intervention name: Pentostatin
description: Intravenous
arm group label: COH-MC-17 and immunosuppressants
other name: NIPENT
intervention type: Drug
intervention name: Rabbit anti-thymocyte globulin
description: Intravenous
arm group label: COH-MC-17 and immunosuppressants
other name: Rabbit ATG
other name: Thymoglobulin
intervention type: Drug
intervention name: Tacrolimus
description: Initially IV. If patient tolerates, convert to oral.
arm group label: COH-MC-17 and immunosuppressants
other name: PROGRAF®
intervention type: Drug
intervention name: Mycophenolate mofetil
description: IV or oral
arm group label: COH-MC-17 and immunosuppressants
other name: MMF
other name: CellCept®
other name: Myfortic
intervention type: Biological
intervention name: CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant
description: Infusion
arm group label: COH-MC-17 and immunosuppressants
other name: CD4+ T-cell depleted HaploHCT
other name: CD4+ T-cell depleted hematopoietic progenitor cell (HPC) product
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Joseph Rosenthal, MD
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Thalassemia
mesh term: Hemoglobinopathies
mesh term: Mycophenolic Acid
mesh term: Cyclophosphamide
mesh term: Pentostatin
mesh term: Tacrolimus
mesh term: Thymoglobulin
mesh term: Antilymphocyte Serum