<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/NCT03754764</url>
  </required_header>
  <id_info>
    <org_study_id>CHN-PLAGH-BT-038</org_study_id>
    <nct_id>NCT03754764</nct_id>
  </id_info>
  <brief_title>A Feasibility and Safety Study of CD38 CAR-T Cell Immunotherapy for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy</brief_title>
  <official_title>Phase I/II Study to Evaluate Treatment of Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy With CAR-T Cells Targeting CD38</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>
      CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or&#xD;
      refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19&#xD;
      in tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells&#xD;
      through recognition of CD38. This is a phase 1/2 study designed to determine the safety of&#xD;
      the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat&#xD;
      patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular&#xD;
      immunotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. PRIMARY OBJECTIVES:&#xD;
&#xD;
             1. To evaluate the feasibility and safety of specificity CD38 CAR-T cells in patients&#xD;
                with relapsed or refractory leukemia and lymphoma.&#xD;
&#xD;
             2. To evaluate the duration of in vivo persistence of adoptively transferred T cells,&#xD;
                and the phenotype of persisting T cells.&#xD;
&#xD;
           Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM&#xD;
           and lymph node will be used to detect and quantify survival of CD38 CAR-T cells over&#xD;
           time.&#xD;
&#xD;
        2. SECONDARY OBJECTIVES:&#xD;
&#xD;
             1. For patients with detectable disease, measure anti-tumor response due to&#xD;
                specificity CD38 CAR-T cell infusions.&#xD;
&#xD;
             2. The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a&#xD;
                using Day 0: 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">November 23, 2018</start_date>
  <completion_date type="Anticipated">November 23, 2022</completion_date>
  <primary_completion_date type="Anticipated">November 23, 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>24 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD of specificity CD38 CAR-T cells</measure>
    <time_frame>4 weeks</time_frame>
    <description>The highest dose of specificity CD38 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 specificity CD38 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>Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T ACI</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Specificity CD38 CAR-T Cells</intervention_name>
    <description>1) Biological: Specificity CD38 CAR-T Cells 2) Day 0: 1-5x10e6/kg total dose .3) Other: Laboratory Biomarker Analysis</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 CD38+ B-cell acute lymphoblastic leukemia after CD19 CAR-T&#xD;
             adoptive cellular immunotherapy&#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>Hejin Jia</last_name>
    <phone>86-10-55499341</phone>
    <email>PLAGH@QQ.COM</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhitao Gao, Dr</last_name>
    <phone>86-010-66937917</phone>
    <email>zhitaogao@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Biotherapeutic Department and Hematology Department of Chinese PLA</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100083</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weidong Han, Dr</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>November 24, 2018</study_first_submitted>
  <study_first_submitted_qc>November 24, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 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>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03754764
org study id: CHN-PLAGH-BT-038
nct id: NCT03754764
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or
      refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19
      in tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells
      through recognition of CD38. This is a phase 1/2 study designed to determine the safety of
      the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat
      patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular
      immunotherapy.
1. PRIMARY OBJECTIVES:

             1. To evaluate the feasibility and safety of specificity CD38 CAR-T cells in patients
                with relapsed or refractory leukemia and lymphoma.

             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 CD38 CAR-T cells over
           time.

        2. SECONDARY OBJECTIVES:

             1. For patients with detectable disease, measure anti-tumor response due to
                specificity CD38 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: 24 weeks
measure: MTD of specificity CD38 CAR-T cells
time frame: 4 weeks
description: The highest dose of specificity CD38 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 specificity CD38 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: Specificity CD38 CAR-T Cells
description: 1) Biological: Specificity CD38 CAR-T Cells 2) Day 0: 1-5x10e6/kg total dose .3) Other: Laboratory Biomarker Analysis
criteria: 
gender: All
minimum age: 12 Years
maximum age: 70 Years
healthy volunteers: No
last name: Hejin Jia
phone: 86-10-55499341
email: PLAGH@QQ.COM
last name: Zhitao Gao, Dr
phone: 86-010-66937917
email: zhitaogao@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: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
sharing ipd: Undecided