<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/NCT03299738</url>
  </required_header>
  <id_info>
    <org_study_id>CBMG-C2017006</org_study_id>
    <nct_id>NCT03299738</nct_id>
  </id_info>
  <brief_title>A Study Evaluating Safety and Efficacy of C-CAR011 in Subjects With B-NHL</brief_title>
  <official_title>A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 in Subjects With B-cell Non-Hodgkin Lymphoma (NHL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cellular Biomedicine Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tianjin Medical University Cancer Institute and Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cellular Biomedicine Group Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a single arm, single-center, non-randomized study to evaluate the safety and efficacy&#xD;
      of C-CAR011 in relapsed or refractory B cell Non-Hodgkin Lymphoma (NHL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will include the following sequential phases: Screening, Pre-Treatment (Cell&#xD;
      Product Preparation, Lymphodepleting Chemotherapy), Treatment and Follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 2017</start_date>
  <completion_date type="Anticipated">August 2019</completion_date>
  <primary_completion_date type="Anticipated">December 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>Safety: Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of remission (DOR)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Refractory or Relapsed B-cell Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>C-CAR011</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>C-CAR011</intervention_name>
    <description>Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously at a target dose of 0.5-5.0 x 10^6 anti-CD19 CAR+ T cells/kg</description>
    <arm_group_label>C-CAR011</arm_group_label>
    <other_name>Anti-CD19 Chimeric Antigen Receptor T cell</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Volunteered to participate in this study and signed informed consent&#xD;
&#xD;
          2. Age 18-70 years old, male or female&#xD;
&#xD;
          3. Relapse or refractory B cell non-Hodgkin's lymphoma&#xD;
&#xD;
               -  1. Histologically diagnosed as DLBCL (including PMBCL) or follicular lymphoma&#xD;
                  (grade Ⅲb) according to the NCCN non-Hodgkin's lymphoma Clinical Practice&#xD;
                  Guidelines (2017 Version 1)&#xD;
&#xD;
                    -  Progressive disease after the last standard chemotherapy regimens per the&#xD;
                       IWG Response Criteria (1999)&#xD;
&#xD;
                    -  Stable disease after the last standard chemotherapy regimens (at least 4&#xD;
                       cycles of first-line therapy or 2 cycles of later-line therapy) per the IWG&#xD;
                       Response Criteria (1999)&#xD;
&#xD;
                    -  Relapse or progressive disease within 12 months after autologous stem cell&#xD;
                       transplantation (SCT)&#xD;
&#xD;
               -  2. Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa)&#xD;
&#xD;
                    -  At least 2 combination chemotherapy regimens (excluding single agent&#xD;
                       monoclonal antibody)&#xD;
&#xD;
                    -  Relapse or progressive disease within 1 year after last chemotherapy&#xD;
                       regimens&#xD;
&#xD;
               -  3. Mantle cell lymphoma&#xD;
&#xD;
                    -  Relapse after 1st CR or persistent disease, and not eligible or appropriate&#xD;
                       for SCT&#xD;
&#xD;
                    -  Relapse or progressive disease within 1 year after the last chemotherapy&#xD;
                       regimens&#xD;
&#xD;
                    -  Relapse or progressive disease within 12 months after autologous SCT&#xD;
&#xD;
          4. All subjects must have received anti-CD20 monoclonal antibody (unless tumor is&#xD;
             CD20-negative) and anthracycline-containing chemotherapy regimens according to NCCN&#xD;
             non-Hodgkin lymphoma Clinical Practice Guidelines (2017 Version 1)&#xD;
&#xD;
          5. At least one measurable lesion per revised IWG Response Criteria (the longest diameter&#xD;
             of the tumor ≥ 1.5 cm)&#xD;
&#xD;
          6. Expected survival ≥ 12 weeks&#xD;
&#xD;
          7. ECOG score 0-1&#xD;
&#xD;
          8. Left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography)&#xD;
&#xD;
          9. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92%&#xD;
             on room air&#xD;
&#xD;
         10. At least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy)&#xD;
             prior to leukapheresis, or at least 4 weeks from monoclonal antibody therapy prior to&#xD;
             CAR T cell therapy&#xD;
&#xD;
         11. No contraindications of leukapheresis&#xD;
&#xD;
         12. 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;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of allergy to cellular products&#xD;
&#xD;
          2. Laboratory tests: absolute neutrophil count &lt; 1.0 × 10^9 /L, platelet count &lt; 50 ×&#xD;
             10^9 /L, serum albumin &lt; 30 g/L, serum bilirubin &gt; 1.5 ULN, serum creatinine &gt; ULN,&#xD;
             ALT/AST &gt; 3 ULN&#xD;
&#xD;
          3. History of CAR T cell therapy or any other genetically modified T cell therapy&#xD;
&#xD;
          4. Relapse after allogeneic hematopoietic stem cell transplantation&#xD;
&#xD;
          5. Active infections that require treatment (uncomplicated urinary tract infections and&#xD;
             bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal&#xD;
             treatment are permitted&#xD;
&#xD;
          6. Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as&#xD;
             acquired or congenital immune deficiency diseases, including but not limited to HIV&#xD;
             infection&#xD;
&#xD;
          7. Class III or IV heart failure according to the NYHA Heart Failure Classifications&#xD;
&#xD;
          8. QT interval prolongation ≥ 450 ms&#xD;
&#xD;
          9. History of epilepsy or other central nervous system disorders&#xD;
&#xD;
         10. Evidence of CNS lymphoma by head enhancement scan or magnetic resonance imaging&#xD;
&#xD;
         11. History of other primary cancers, with the following exceptions&#xD;
&#xD;
               -  Excisional non-melanoma (e.g. cutaneous basal cell carcinoma)&#xD;
&#xD;
               -  Cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer)&#xD;
&#xD;
         12. Autoimmune diseases that require treatment, immune deficiency diseases or other&#xD;
             diseases that require immunosuppressive therapy&#xD;
&#xD;
         13. Used of systemic steroids within two weeks (using inhaled steroids is an exception)&#xD;
&#xD;
         14. Women who are pregnant or lactating, or who have breeding intent in 6 months&#xD;
&#xD;
         15. Participated in any other clinical trial within three months&#xD;
&#xD;
         16. Any situation that investigators believe the risk of the subjects is increased or&#xD;
             results of the trial are disturbed&#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>Huilai Zhang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Huilai Zhang</last_name>
    <phone>+86-022-23340123</phone>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital</name>
      <address>
        <city>Tianjin</city>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Huilai Zhang</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>December 18, 2017</last_update_submitted>
  <last_update_submitted_qc>December 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</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/NCT03299738
org study id: CBMG-C2017006
nct id: NCT03299738
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single arm, single-center, non-randomized study to evaluate the safety and efficacy
      of C-CAR011 in relapsed or refractory B cell Non-Hodgkin Lymphoma (NHL).
The study will include the following sequential phases: Screening, Pre-Treatment (Cell
      Product Preparation, Lymphodepleting Chemotherapy), Treatment and Follow-up.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs)
time frame: 12 weeks
description: Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs)
measure: Overall response rate (ORR)
time frame: 12 weeks
measure: Overall response rate (ORR)
time frame: 6 months
measure: Overall response rate (ORR)
time frame: 12 months
measure: Duration of remission (DOR)
time frame: 12 months
measure: Progression free survival (PFS)
time frame: 12 months
measure: Overall survival (OS)
time frame: 12 months
arm group label: C-CAR011
arm group type: Experimental
description: Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene
intervention type: Biological
intervention name: C-CAR011
description: Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously at a target dose of 0.5-5.0 x 10^6 anti-CD19 CAR+ T cells/kg
arm group label: C-CAR011
other name: Anti-CD19 Chimeric Antigen Receptor T cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Huilai Zhang
role: Principal Investigator
affiliation: Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital
last name: Huilai Zhang
phone: +86-022-23340123
facility: 
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
sharing ipd: Undecided