<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/NCT03301168</url>
  </required_header>
  <id_info>
    <org_study_id>BP-U-004</org_study_id>
    <nct_id>NCT03301168</nct_id>
  </id_info>
  <brief_title>Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant</brief_title>
  <official_title>Phase I/II Study of CaspaCIDe® T Cells From an HLA-Partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate pediatric patients with malignant or non-malignant blood cell&#xD;
      disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa&#xD;
      and beta cells that comes from a partially matched family donor. The study will assess&#xD;
      whether immune cells, called T cells, from the family donor, that are specially grown in the&#xD;
      laboratory and given back to the patient along with the stem cell transplant can help the&#xD;
      immune system recover faster after transplant. As a safety measure these T cells have been&#xD;
      programmed with a self-destruct switch so that they can be destroyed if they start to react&#xD;
      against tissues (graft versus host disease).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1/2 study evaluating the safety and feasibility of BPX-501 T cells infused&#xD;
      after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell&#xD;
      transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine&#xD;
      whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic&#xD;
      disorders, with the potential for reducing the severity and duration severe acute graft&#xD;
      versus host disease (GvHD).&#xD;
&#xD;
      The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug&#xD;
      (AP1903/rimiducid) in those subjects who present with GVHD that does not adequately respond&#xD;
      to standard of care therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 2014</start_date>
  <completion_date type="Anticipated">May 2034</completion_date>
  <primary_completion_date type="Actual">May 11, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</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 Event</measure>
    <time_frame>Month 24</time_frame>
    <description>Demonstrate safety of BPX-501 MTD</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TRM/NRM</measure>
    <time_frame>Day 180, Month 12</time_frame>
    <description>Assess the cumulative incidence of non-relapse/transplant related mortality</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>Month 24</time_frame>
    <description>Disease-free survival rates after transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse</measure>
    <time_frame>Month 12</time_frame>
    <description>Cumulative incidence of relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Engraftment</measure>
    <time_frame>Month 24</time_frame>
    <description>Cumulative incidence of neutrophil and platelet engraftment, primary &amp; secondary graft failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GvHD</measure>
    <time_frame>Month 24</time_frame>
    <description>Cumulative incidence and severity of acute and chronic GvHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rimiducid Efficacy</measure>
    <time_frame>Month 24</time_frame>
    <description>Time to resolution of acute or chronic GvHD after administration of rimiducid</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection</measure>
    <time_frame>Month 24</time_frame>
    <description>Rate of infectious complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalizations</measure>
    <time_frame>Month 24</time_frame>
    <description>Duration of hospitalization and rehospitalization</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Acute Lymphoblastic Leukemia</condition>
  <condition>Leukemia, Acute Myeloid (AML), Child</condition>
  <condition>Lymphoma, Non-Hodgkin</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Primary Immune Deficiency Disorder</condition>
  <condition>Osteopetrosis</condition>
  <condition>Cytopenia</condition>
  <condition>Hemoglobinopathy in Children</condition>
  <condition>Anemia, Aplastic</condition>
  <arm_group>
    <arm_group_label>BPX-501 T cells and Rimiducid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TCR alpha beta depleted graft infusion with addback of BPX-501 T cells.&#xD;
Rimiducid: Dimerizer drug administered to subjects who present with Grade I-IV acute GVHD with inadequate response to steroids within 48 hours of treatment or mild to severe chronic GVHD with inadequate response to steroids within 7 days of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BPX-501 T cells</intervention_name>
    <description>T cells transduced with CaspaCIDe® safety switch</description>
    <arm_group_label>BPX-501 T cells and Rimiducid</arm_group_label>
    <other_name>rivogenlecleucel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rimiducid</intervention_name>
    <description>administered to inactivate BPX-501 cells in the event of GVHD</description>
    <arm_group_label>BPX-501 T cells and Rimiducid</arm_group_label>
    <other_name>AP1903</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 1 month and &lt; 26 years&#xD;
&#xD;
          2. Life expectancy &gt; 10 weeks&#xD;
&#xD;
          3. Subjects deemed eligible for allogeneic stem cell transplantation.&#xD;
&#xD;
          4. Subjects with life-threatening hematological malignancies (high-risk ALL in 1st CR,&#xD;
             ALL in 2nd or subsequent CR, AML in 1st CR, AML in 2nd or subsequent CR,&#xD;
             myelodysplastic syndromes, non-Hodgkin lymphomas in 2nd or subsequent CR, other&#xD;
             hematologic malignancies eligible for stem cell transplantation per institutional&#xD;
             standard);&#xD;
&#xD;
          5. Non-malignant disorders amenable to cure by an allograft:&#xD;
&#xD;
               1. primary immune deficiencies,&#xD;
&#xD;
               2. severe aplastic anemia not responding to immune suppressive therapy,&#xD;
&#xD;
               3. osteopetrosis,&#xD;
&#xD;
               4. hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan&#xD;
                  anemia among others)&#xD;
&#xD;
               5. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal&#xD;
                  malignant evolution (MDS, AML) Note: Subjects will be eligible if they meet&#xD;
                  either item 4 OR item 5.&#xD;
&#xD;
          6. Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically&#xD;
             identical relative or 10/10 unrelated donor evaluated using high resolution molecular&#xD;
             typing) or presence of rapidly progressive disease not permitting time to identify an&#xD;
             unrelated donor&#xD;
&#xD;
          7. A minimum genotypic identical match of 5/ 10 is required.&#xD;
&#xD;
          8. The donor and recipient must be identical, as determined by high resolution typing, at&#xD;
             least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-&#xD;
             DRB1 and HLA-DQB1.&#xD;
&#xD;
          9. Lansky/Karnofsky score &gt; 50&#xD;
&#xD;
         10. Signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous allograft&#xD;
             at the time of inclusion&#xD;
&#xD;
          2. Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous&#xD;
             allograft at the time of inclusion&#xD;
&#xD;
          3. Dysfunction of liver (ALT/AST &gt; 5 times normal value, or bilirubin &gt; 3 times normal&#xD;
             value), or of renal function (creatinine clearance &lt; 30 mL / min)&#xD;
&#xD;
          4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive&#xD;
             heart failure or left ventricular ejection fraction &lt; 40%)&#xD;
&#xD;
          5. Current active infectious disease (including positive HIV serology or viral RNA)&#xD;
&#xD;
          6. Serious concurrent uncontrolled medical disorder&#xD;
&#xD;
          7. Pregnant or breastfeeding subject&#xD;
&#xD;
          8. For subjects who have received more than 1 x 10E5 alpha/beta T cells/kg with the graft&#xD;
             infusion the clinical trial site must contact the sponsor for approval to be eligible&#xD;
             to receive BPX-501 infusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>26 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bellicum Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Bellicum Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University - Division of Pediatric Stem Cell Transplant &amp; Regenerative Medicine</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</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>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Boston Children's Cancer and Blood Disorders Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital at Montefiore</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health Sciences University - Doernbecher Children's Hospital</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern-Children's Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>77390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine/ Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</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_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</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>ALL</keyword>
  <keyword>AML</keyword>
  <keyword>hematologic neoplasms</keyword>
  <keyword>hematologic malignancies</keyword>
  <keyword>primary immune deficiences</keyword>
  <keyword>allogeneic stem cell transplant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Osteopetrosis</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Hemoglobinopathies</mesh_term>
    <mesh_term>Anemia, Aplastic</mesh_term>
    <mesh_term>Primary Immunodeficiency Diseases</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 22, 2023</submitted>
    <returned>July 13, 2023</returned>
    <submitted>September 12, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03301168
org study id: BP-U-004
nct id: NCT03301168
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will evaluate pediatric patients with malignant or non-malignant blood cell
      disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa
      and beta cells that comes from a partially matched family donor. The study will assess
      whether immune cells, called T cells, from the family donor, that are specially grown in the
      laboratory and given back to the patient along with the stem cell transplant can help the
      immune system recover faster after transplant. As a safety measure these T cells have been
      programmed with a self-destruct switch so that they can be destroyed if they start to react
      against tissues (graft versus host disease).
This is a Phase 1/2 study evaluating the safety and feasibility of BPX-501 T cells infused
      after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell
      transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine
      whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic
      disorders, with the potential for reducing the severity and duration severe acute graft
      versus host disease (GvHD).

      The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug
      (AP1903/rimiducid) in those subjects who present with GVHD that does not adequately respond
      to standard of care therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Event
time frame: Month 24
description: Demonstrate safety of BPX-501 MTD
measure: TRM/NRM
time frame: Day 180, Month 12
description: Assess the cumulative incidence of non-relapse/transplant related mortality
measure: Disease-free survival
time frame: Month 24
description: Disease-free survival rates after transplantation
measure: Relapse
time frame: Month 12
description: Cumulative incidence of relapse
measure: Engraftment
time frame: Month 24
description: Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure
measure: GvHD
time frame: Month 24
description: Cumulative incidence and severity of acute and chronic GvHD
measure: Rimiducid Efficacy
time frame: Month 24
description: Time to resolution of acute or chronic GvHD after administration of rimiducid
measure: Infection
time frame: Month 24
description: Rate of infectious complications
measure: Hospitalizations
time frame: Month 24
description: Duration of hospitalization and rehospitalization
arm group label: BPX-501 T cells and Rimiducid
arm group type: Experimental
description: TCR alpha beta depleted graft infusion with addback of BPX-501 T cells.
Rimiducid: Dimerizer drug administered to subjects who present with Grade I-IV acute GVHD with inadequate response to steroids within 48 hours of treatment or mild to severe chronic GVHD with inadequate response to steroids within 7 days of treatment.
intervention type: Biological
intervention name: BPX-501 T cells
description: T cells transduced with CaspaCIDe® safety switch
arm group label: BPX-501 T cells and Rimiducid
other name: rivogenlecleucel
intervention type: Drug
intervention name: Rimiducid
description: administered to inactivate BPX-501 cells in the event of GVHD
arm group label: BPX-501 T cells and Rimiducid
other name: AP1903
criteria: 
gender: All
minimum age: 1 Month
maximum age: 26 Years
healthy volunteers: No
last name: Bellicum Pharmaceuticals
role: Study Director
affiliation: Bellicum Pharmaceuticals, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
country: Italy
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Myeloid, Acute
mesh term: Osteopetrosis
mesh term: Myelodysplastic Syndromes
mesh term: Hemoglobinopathies
mesh term: Anemia, Aplastic
mesh term: Primary Immunodeficiency Diseases
mesh term: Immunologic Deficiency Syndromes
sharing ipd: No
submitted: June 22, 2023
returned: July 13, 2023
submitted: September 12, 2023