<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/NCT03767751</url>
  </required_header>
  <id_info>
    <org_study_id>CHN-PLAGH-BT-037</org_study_id>
    <nct_id>NCT03767751</nct_id>
  </id_info>
  <brief_title>A Feasibility and Safety Study of Dual Specificity CD38 and BCMA CAR-T Cell Immunotherapy for Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>Phase I/II Study to Evaluate Treatment of Relapsed or Refractory Multiple Myeloma With Dual CAR-T Cells Targeting CD38 and BCMA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese PLA General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory&#xD;
      Multiple Myeloma,however, a subset of patients relapse due to the loss of target in tumor&#xD;
      cells.Dual Specificity CD38 and BCMA CAR-T cells can recognize and kill the malignant cells&#xD;
      through recognition of CD38 or BCMA. This is a phase 1/2 study designed to determine the&#xD;
      safety of dual specificity CD38 and BCMA CAR-T cells and the feasibility of making enough to&#xD;
      treat patients with relapsed or refractory Multiple Myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. PRIMARY OBJECTIVES:&#xD;
&#xD;
             1. To evaluate the feasibility and safety of dual specificity CD38 and BCMA CAR-T&#xD;
                cells in patients with relapsed or refractory Multiple Myeloma.&#xD;
&#xD;
             2. To evaluate the duration of in vivo persistence of adoptively transferred T cells,&#xD;
                and the phenotype of persisting T cells.Real Time polymerase chain receptor&#xD;
                (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to&#xD;
                detect and quantify survival of universal dual specificity CD38 and BCMA CAR-T&#xD;
                cells over time.&#xD;
&#xD;
        2. SECONDARY OBJECTIVES:&#xD;
&#xD;
      1.For patients with detectable disease, measure anti-tumor response due to dual specificity&#xD;
      CD38 and BCMA CAR-T cell infusions.&#xD;
&#xD;
      2.The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0:&#xD;
      1-5x10e6/kg total dose on day 0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 5, 2018</start_date>
  <completion_date type="Anticipated">December 5, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 5, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>24weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD of dual specificity CD38 and BCMA CAR-T cells</measure>
    <time_frame>4 weeks</time_frame>
    <description>The highest dose of dual specificity CD38 and BCMA CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of dual specificity CD38 and BCMA CAR-T cells</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes</measure>
    <time_frame>24 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Six-month Objective response rate of complete remission and partial remission</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six-month Overall survival</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six-month Progression free survival</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Multiple Myeloma</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Dual Specificity CD38 and bcma CAR-T Cells</intervention_name>
    <description>1) Biological: Dual Specificity CD38 and BCMA CAR-T Cells,2)1-5X10E6/Kg</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female participant&#xD;
&#xD;
          2. 12 Years to 70 Years (Child, Adult, Senior)&#xD;
&#xD;
          3. Patient with relapsed or refractory Multiple Myeloma,multiple myeloma cell express&#xD;
             CD38(over 50%) and BCMA (over 50%)&#xD;
&#xD;
          4. Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
&#xD;
          6. Adequate organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative&#xD;
             intent and with no evidence of active disease&#xD;
&#xD;
          2. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic&#xD;
             myelogenous leukemia lymphoid blast crisis&#xD;
&#xD;
          3. Richter's syndrome&#xD;
&#xD;
          4. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at&#xD;
             the time of screening&#xD;
&#xD;
          5. Subjects with any autoimmune disease or any immune deficiency disease or other disease&#xD;
             in need of immunosuppressive therapy&#xD;
&#xD;
          6. Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis&#xD;
             is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is&#xD;
             permissible&#xD;
&#xD;
          7. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV)&#xD;
             infection at the time of screening&#xD;
&#xD;
          8. Patient has an investigational medicinal product within the last 30 days prior to&#xD;
             screening&#xD;
&#xD;
          9. Previous treatment with investigational gene or cell therapy medicine products&#xD;
&#xD;
         10. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not&#xD;
             exclusionary&#xD;
&#xD;
         11. Pregnant or nursing women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>YaJing Zhang</last_name>
    <phone>86-10-55499341</phone>
    <email>plagh@qq.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weidong Han</last_name>
      <phone>86-10-13651392893</phone>
      <email>hanwdrsw@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>December 5, 2018</last_update_submitted>
  <last_update_submitted_qc>December 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Han weidong</investigator_full_name>
    <investigator_title>Director of Molecular &amp; Immunological Department,Biotherapeutic Department</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_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/NCT03767751
org study id: CHN-PLAGH-BT-037
nct id: NCT03767751
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory
      Multiple Myeloma,however, a subset of patients relapse due to the loss of target in tumor
      cells.Dual Specificity CD38 and BCMA CAR-T cells can recognize and kill the malignant cells
      through recognition of CD38 or BCMA. This is a phase 1/2 study designed to determine the
      safety of dual specificity CD38 and BCMA CAR-T cells and the feasibility of making enough to
      treat patients with relapsed or refractory Multiple Myeloma.
1. PRIMARY OBJECTIVES:

             1. To evaluate the feasibility and safety of dual specificity CD38 and BCMA CAR-T
                cells in patients with relapsed or refractory Multiple Myeloma.

             2. To evaluate the duration of in vivo persistence of adoptively transferred T cells,
                and the phenotype of persisting T cells.Real Time polymerase chain receptor
                (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to
                detect and quantify survival of universal dual specificity CD38 and BCMA CAR-T
                cells over time.

        2. SECONDARY OBJECTIVES:

      1.For patients with detectable disease, measure anti-tumor response due to dual specificity
      CD38 and BCMA CAR-T cell infusions.

      2.The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0:
      1-5x10e6/kg total dose on day 0.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
time frame: 24weeks
measure: MTD of dual specificity CD38 and BCMA CAR-T cells
time frame: 4 weeks
description: The highest dose of dual specificity CD38 and BCMA CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of dual specificity CD38 and BCMA CAR-T cells
measure: Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
time frame: 24 weeks
measure: Six-month Objective response rate of complete remission and partial remission
time frame: 24 weeks
measure: Six-month Overall survival
time frame: 24 weeks
measure: Six-month Progression free survival
time frame: 24 weeks
intervention type: Biological
intervention name: Dual Specificity CD38 and bcma CAR-T Cells
description: 1) Biological: Dual Specificity CD38 and BCMA CAR-T Cells,2)1-5X10E6/Kg
criteria: 
gender: All
minimum age: 12 Years
maximum age: 70 Years
healthy volunteers: No
last name: YaJing Zhang
phone: 86-10-55499341
email: plagh@qq.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Han weidong
investigator title: Director of Molecular & Immunological Department,Biotherapeutic Department
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell