<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/NCT02231710</url>
  </required_header>
  <id_info>
    <org_study_id>BP-003</org_study_id>
    <nct_id>NCT02231710</nct_id>
  </id_info>
  <brief_title>Safety Study of Gene Modified Donor T Cell Infusion After Stem Cell Transplant for Non-Malignant Diseases</brief_title>
  <official_title>A Study Evaluating BPX-501 T Cells and AP1903 for Prevention of Graft Versus Host Disease (GVHD) After Haploidentical, Related, T Cell-Depleted Hematopoietic Cell Transplantation for Non-Malignant Diseases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bellicum Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bellicum Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this study is to determine a safe dose of BPX-501 gene modified T cells&#xD;
      infused after a haplo-identical stem cell transplant to facilitate engraftment and the safety&#xD;
      of Rimiducid (AP1903) on day 7 to prevent GVHD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm dose finding study evaluating the safety and efficacy of a BPX 501&#xD;
      infusion (T cells genetically modified with the inducible Caspase 9 suicide gene) of 3x10E6&#xD;
      to 1X10E7 cells/kg followed by a Rimiducid infusion on day 7 after a partially mismatched,&#xD;
      related, T cell-depleted hematopoietic cell transplantation (HCT) in patients with&#xD;
      non-malignant diseases. The purpose of this clinical trial is to determine the dose of BPX&#xD;
      501 T cell infusion with subsequent planned infusion of Rimiducid which can facilitate&#xD;
      engraftment and prevent the occurrence of GVHD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 2015</start_date>
  <completion_date type="Anticipated">July 2030</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</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>Adverse Events</measure>
    <time_frame>Month 24</time_frame>
    <description>Determine the safety of HCT with HLA-haploidentical CD34+ selected peripheral blood stem cell (PBSC) grafts and BPX 501 T cells followed by scheduled AP1903 infusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Engraftment</measure>
    <time_frame>Day 28</time_frame>
    <description>Determine the engraftment rate (defined as &gt;50% donor CD3 chimerism) on day 28 after HCT with HLA-haploidentical CD34+ selected PBSC grafts per dose cohort of BPX 501 T cells followed by Rimiducid infusion on Day 7.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>GvHD</measure>
    <time_frame>Month 24</time_frame>
    <description>To determine the incidence and severity of acute and chronic GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune Reconstitution</measure>
    <time_frame>Month 24</time_frame>
    <description>Measure immune reconstitution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection rates</measure>
    <time_frame>Day 200</time_frame>
    <description>Determine the risk for severe infections</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft rejection</measure>
    <time_frame>Month 24</time_frame>
    <description>Incidence of graft rejection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rimiducid Activity</measure>
    <time_frame>Month 24</time_frame>
    <description>Time to resolution of acute and chronic GvHD following administration of Rimiducid</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High grade toxicity</measure>
    <time_frame>Month 24</time_frame>
    <description>Rate of high grade toxicity</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Primary Immune Deficiency Disorders</condition>
  <condition>Hemophagocytic Lymphohistiocytosis</condition>
  <condition>Inherited Bone Marrow Failure Syndrome</condition>
  <condition>Hemoglobinopathies</condition>
  <condition>Metabolic Disorders</condition>
  <arm_group>
    <arm_group_label>BPX-501 and Rimiducid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BPX-501 and Rimiducid</intervention_name>
    <description>Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7</description>
    <arm_group_label>BPX-501 and Rimiducid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient must meet eligibility criteria for allogeneic transplantation&#xD;
&#xD;
          2. Lack of suitable conventional donor (10/10 allele matched related or unrelated donor)&#xD;
             or presence of rapidly progressive disease not permitting time to identify an&#xD;
             unrelated donor&#xD;
&#xD;
          3. Males or females&#xD;
&#xD;
          4. Age &lt; 55 years old and &gt; 4 months&#xD;
&#xD;
          5. Diagnosis of a nonmalignant disorder considered treatable by HCT.&#xD;
&#xD;
          6. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw,&#xD;
             DRBl, and DQB1 loci.&#xD;
&#xD;
             i. A minimum match of 5/10 is required. ii. The donor and recipient must be identical,&#xD;
             as determined by high resolution typing, in at least one allele of each of the&#xD;
             following&#xD;
&#xD;
          7. If capable of reproduction, patient must agree to use contraception or abstinence to&#xD;
             prevent pregnancy during the first year of enrollment and treatment.&#xD;
&#xD;
          8. Informed consent signed by patient (if ≥18 years old) or parent/guardian (if &lt;18 years&#xD;
             old).&#xD;
&#xD;
          9. Fanconi anemia patients ONLY i) Patients must meet one of the following criteria to be&#xD;
             eligible for this study:&#xD;
&#xD;
               1. Any patient with Fanconi anemia and bone marrow failure involving 2 of the&#xD;
                  following 3 lineages: granulocyte count &lt;0.5 x 109/L, platelet count &lt;20 x 109/L,&#xD;
                  or hemoglobin &lt;8 g/dL.&#xD;
&#xD;
               2. Any patient with Fanconi anemia who requires red blood cell or platelet&#xD;
                  transfusions because of marrow failure&#xD;
&#xD;
               3. Any patient with Fanconi anemia who has a life-threatening bone marrow failure&#xD;
                  involving a single hematopoietic lineage.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serious organ dysfunction&#xD;
&#xD;
          2. Pregnant or breast-feeding&#xD;
&#xD;
          3. Evidence of HIV infection&#xD;
&#xD;
          4. Bovine product allergy&#xD;
&#xD;
          5. Patients with an active infectious disease&#xD;
&#xD;
          6. Patients with Fanconi anemia with AML/MDS.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Months</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bellicum Pharmaceuticals Senior Director</last_name>
    <role>Study Director</role>
    <affiliation>Clinical Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer ResearchCenter</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>July 10, 2022</last_update_submitted>
  <last_update_submitted_qc>July 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Severe Combined Immune Deficiency</keyword>
  <keyword>Congenital T-cell Defect</keyword>
  <keyword>Congenital T-cell Deficiency</keyword>
  <keyword>Chronic Granulomatous Disease</keyword>
  <keyword>Shwachman Diamond Syndrome</keyword>
  <keyword>Diamond Blackfan Anemia</keyword>
  <keyword>Dyskeratosis Congenita</keyword>
  <keyword>Fanconi Anemia</keyword>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Thalassemia</keyword>
  <keyword>Mucopolysaccharidosis</keyword>
  <keyword>Sphingolipidoses</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bone Marrow Failure Disorders</mesh_term>
    <mesh_term>Pancytopenia</mesh_term>
    <mesh_term>Hemoglobinopathies</mesh_term>
    <mesh_term>Lymphohistiocytosis, Hemophagocytic</mesh_term>
    <mesh_term>Congenital Bone Marrow Failure Syndromes</mesh_term>
    <mesh_term>Primary Immunodeficiency Diseases</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_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/NCT02231710
org study id: BP-003
nct id: NCT02231710
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine a safe dose of BPX-501 gene modified T cells
      infused after a haplo-identical stem cell transplant to facilitate engraftment and the safety
      of Rimiducid (AP1903) on day 7 to prevent GVHD.
This is a single arm dose finding study evaluating the safety and efficacy of a BPX 501
      infusion (T cells genetically modified with the inducible Caspase 9 suicide gene) of 3x10E6
      to 1X10E7 cells/kg followed by a Rimiducid infusion on day 7 after a partially mismatched,
      related, T cell-depleted hematopoietic cell transplantation (HCT) in patients with
      non-malignant diseases. The purpose of this clinical trial is to determine the dose of BPX
      501 T cell infusion with subsequent planned infusion of Rimiducid which can facilitate
      engraftment and prevent the occurrence of GVHD.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: Month 24
description: Determine the safety of HCT with HLA-haploidentical CD34+ selected peripheral blood stem cell (PBSC) grafts and BPX 501 T cells followed by scheduled AP1903 infusion
measure: Engraftment
time frame: Day 28
description: Determine the engraftment rate (defined as >50% donor CD3 chimerism) on day 28 after HCT with HLA-haploidentical CD34+ selected PBSC grafts per dose cohort of BPX 501 T cells followed by Rimiducid infusion on Day 7.
measure: GvHD
time frame: Month 24
description: To determine the incidence and severity of acute and chronic GVHD
measure: Immune Reconstitution
time frame: Month 24
description: Measure immune reconstitution
measure: Infection rates
time frame: Day 200
description: Determine the risk for severe infections
measure: Graft rejection
time frame: Month 24
description: Incidence of graft rejection
measure: Rimiducid Activity
time frame: Month 24
description: Time to resolution of acute and chronic GvHD following administration of Rimiducid
measure: High grade toxicity
time frame: Month 24
description: Rate of high grade toxicity
arm group label: BPX-501 and Rimiducid
arm group type: Experimental
description: Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7
intervention type: Biological
intervention name: BPX-501 and Rimiducid
description: Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7
arm group label: BPX-501 and Rimiducid
criteria: 
gender: All
minimum age: 4 Months
maximum age: 55 Years
healthy volunteers: No
last name: Bellicum Pharmaceuticals Senior Director
role: Study Director
affiliation: Clinical Development
facility: 
country: United States
responsible party type: Sponsor
mesh term: Bone Marrow Failure Disorders
mesh term: Pancytopenia
mesh term: Hemoglobinopathies
mesh term: Lymphohistiocytosis, Hemophagocytic
mesh term: Congenital Bone Marrow Failure Syndromes
mesh term: Primary Immunodeficiency Diseases
mesh term: Metabolic Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: No