<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/NCT02976857</url>
  </required_header>
  <id_info>
    <org_study_id>CBMG2016002</org_study_id>
    <nct_id>NCT02976857</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 Treatment in DLBCL Subjects</brief_title>
  <acronym>C-CAR011</acronym>
  <official_title>A Phase 1 Single Center, Non-randomized Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Refractory Diffuse Large B-cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cellular Biomedicine Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cellular Biomedicine Group Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial is a single arm, single-center, non-randomized phase I clinical trial which is&#xD;
      designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The 3x3 dose escalation design will be adopted in order to determine the maximum tolerated&#xD;
      dose (MTD). Subjects will be enrolled into low-dose group, medium-dose group and high-dose&#xD;
      group as below:&#xD;
&#xD;
      Dose CAR+ cells/kg&#xD;
&#xD;
      Low 0.8×106&#xD;
&#xD;
      Medium 2.5×106&#xD;
&#xD;
      High 5.0×106&#xD;
&#xD;
      DLT is evaluated within 30 days post C-CAR011 infusion).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">January 9, 2019</completion_date>
  <primary_completion_date type="Actual">September 11, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</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>Dose-limiting toxicity (DLT)</measure>
    <time_frame>28 days</time_frame>
    <description>Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of C-CAR011 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (&lt;72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>4 and 12 weeks</time_frame>
    <description>Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 4 and weeks 12 according to International Working Group (IWG) revised criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Disease control rate (DCR） = complete response (CR) rate + partial response (PR) rate + stable disease (SD) rate, DCR will be assessed at weeks 12 according to International Working Group (IWG) revised criteria.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Refractory Diffuse Large B-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>C-CAR011</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>C-CAR-011</intervention_name>
    <description>lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene.</description>
    <arm_group_label>C-CAR011</arm_group_label>
    <other_name>CAR-CD19</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma&#xD;
             Clinical Practice Guidelines (3rd edition 2016)&#xD;
&#xD;
          -  Refractory DLBCL&#xD;
&#xD;
          -  All subjects must have received adequate prior therapy including anti-CD20 monoclonal&#xD;
             antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy&#xD;
             regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma&#xD;
             Clinical Practice Guidelines (2016 Version 3)&#xD;
&#xD;
          -  At least one measurable lesion per revised IWG Response Criteria (the longest diameter&#xD;
             of the tumor ≥ 1.5 cm)&#xD;
&#xD;
          -  Age 18-70 years old, male or female&#xD;
&#xD;
          -  Expected survival ≥ 12 weeks&#xD;
&#xD;
          -  ECOG score 0-1&#xD;
&#xD;
          -  Subject's left ventricular ejection fraction (LVEF) is ≥ 50% and no evidence of&#xD;
             pericardial effusion as determined by an ECHO&#xD;
&#xD;
          -  At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy,&#xD;
             monoclonal antibody therapy or other treatments)&#xD;
&#xD;
          -  No contraindications of peripheral blood apheresis&#xD;
&#xD;
          -  Female subjects in childbearing age, their serum or urine pregnancy test must be&#xD;
             negative, and must agree to take effective contraceptive measures during the trial&#xD;
             measures&#xD;
&#xD;
          -  Volunteered to participate in this study and signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have a history of allergy to cellular products&#xD;
&#xD;
          -  Used any genetically modified T cell therapy&#xD;
&#xD;
          -  History of allogeneic hematopoietic stem cell transplantation&#xD;
&#xD;
          -  Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis&#xD;
             allowed) or currently receiving intravenous antibiotic therapy and received&#xD;
             intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and&#xD;
             antifungal treatment is permissible&#xD;
&#xD;
          -  Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired,&#xD;
             congenital immune deficiency diseases, including but not limited to HIV-infected&#xD;
             persons&#xD;
&#xD;
          -  Patients with class III and IV heart failure according to the NYHA Heart Failure&#xD;
             Classifications&#xD;
&#xD;
          -  A history of QT prolongation&#xD;
&#xD;
          -  A history of epilepsy or other central nervous system disorders&#xD;
&#xD;
          -  The patient had a history of other primary cancers, with the following exceptions:&#xD;
             Excisional non-melanoma such as cutaneous basal cell carcinoma; Cured in situ&#xD;
             carcinoma such as cervical cancer, bladder cancer or breast cancer&#xD;
&#xD;
          -  Subjects with any autoimmune disease or any immune deficiency disease or other disease&#xD;
             in need of immunosuppressive therapy&#xD;
&#xD;
          -  Used of systemic steroids within two weeks (using inhaled steroids is an exception)&#xD;
&#xD;
          -  Women who are pregnant or lactating or have breeding intent in 6 months&#xD;
&#xD;
          -  Participated in any other clinical trial within three months&#xD;
&#xD;
          -  The investigators believe that any increase in the risk of the subject or interference&#xD;
             with the results of the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianyong Li</last_name>
    <role>Principal Investigator</role>
    <affiliation>The First Affiliated Hospital with Nanjing Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hematological Department, People's Hospital of Jiangsu Province</name>
      <address>
        <city>Nanjing City</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>January 16, 2019</last_update_submitted>
  <last_update_submitted_qc>January 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>refractory diffuse large B-cell lymphoma</keyword>
  <keyword>anti-CD19 chimeric antigen receptor T-cell</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</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/NCT02976857
org study id: CBMG2016002
nct id: NCT02976857
lead sponsor: 
collaborator: 
has dmc: Yes
The trial is a single arm, single-center, non-randomized phase I clinical trial which is
      designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL
The 3x3 dose escalation design will be adopted in order to determine the maximum tolerated
      dose (MTD). Subjects will be enrolled into low-dose group, medium-dose group and high-dose
      group as below:

      Dose CAR+ cells/kg

      Low 0.8×106

      Medium 2.5×106

      High 5.0×106

      DLT is evaluated within 30 days post C-CAR011 infusion).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity (DLT)
time frame: 28 days
description: Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of C-CAR011 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever.
measure: Overall response rate
time frame: 4 and 12 weeks
description: Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 4 and weeks 12 according to International Working Group (IWG) revised criteria.
measure: Disease control rate
time frame: 12 weeks
description: Disease control rate (DCR） = complete response (CR) rate + partial response (PR) rate + stable disease (SD) rate, DCR will be assessed at weeks 12 according to International Working Group (IWG) revised criteria.
arm group label: C-CAR011
arm group type: Experimental
description: C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion.
intervention type: Biological
intervention name: C-CAR-011
description: lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene.
arm group label: C-CAR011
other name: CAR-CD19
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jianyong Li
role: Principal Investigator
affiliation: The First Affiliated Hospital with Nanjing Medical University
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
sharing ipd: Undecided