<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/NCT03018093</url>
  </required_header>
  <id_info>
    <org_study_id>CBMG2016003</org_study_id>
    <nct_id>NCT03018093</nct_id>
  </id_info>
  <brief_title>A Phase I Study Evaluating Safety and Efficacy of C-CAR011 Treatment in Adult Subjects With r/r CD19+B-ALL</brief_title>
  <official_title>A Phase I Study Evaluating Safety and Efficacy of CBM.CD19-targeted Chimeric Antigen Receptor T Cells (C-CAR011) Treatment in Adult Subjects With Relapsed/Refractory CD19+ B Cells Acute Lymphoblastic Leukemia(CALL-1)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cellular Biomedicine Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chinese PLA General Hospital</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 adult subjects with&#xD;
      relapsed/refractory CD19+ B cells acute lymphoblastic leukemia(r/r CD19+B-ALL)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, Open Label phase I clinical trial, 20 subjects planned to be&#xD;
      enrolled. The trial have two stages (Phase I dose-escalation clinical trial and phase I dose&#xD;
      expansion trial).Subjects will be divided into low-dose group, medium-dose group and&#xD;
      high-dose group.Additional patients will be enrolled to confirm the optimal dose&#xD;
&#xD;
      Dose CAR+ cells/kg Low 0.5×106 Medium 1.5×106 High 3.0×106&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">November 2018</completion_date>
  <primary_completion_date type="Anticipated">August 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>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal residual disease negative remission rate(MRD-)</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Relapsed or Refractory Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>C-CAR011</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In day 0, 1 and 2, CAR011 cells will be intravenous infused at the 10%, 30% and 60% ratio respectively.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>C-CAR-011</intervention_name>
    <description>CD19-targeted chimeric antigen receptor T cells</description>
    <arm_group_label>C-CAR011</arm_group_label>
    <other_name>CAR-CD19</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 14-75 years old, male or female.&#xD;
&#xD;
          -  Volunteered to participate in this study and signed written informed consent form.&#xD;
&#xD;
          -  Histologically diagnosed as CD19+B-ALL according to the NCCN Acute Lymphoblastic&#xD;
             Leukemia Clinical Practice Guidelines (2016 version 1).&#xD;
&#xD;
          -  Relapsed or refractory CD19+B-ALL (meet one of the following conditions)&#xD;
&#xD;
               1. Refractory as defined not achieving a CR(complete remission, morphology&lt;5%&#xD;
                  blasts) after two cycles of standard chemotherapy regimen.&#xD;
&#xD;
               2. Duration of remission ≤ 12 months after the first induction chemotherapy regimen.&#xD;
&#xD;
               3. Refractory disease after one or more salvage therapies.&#xD;
&#xD;
               4. Two or more Bone Marrow relapse.&#xD;
&#xD;
          -  Morphological disease in the bone marrow (≥ 5% blasts).&#xD;
&#xD;
          -  Subjects with Philadelphia chromosome negative(Ph-) disease, or subjects with&#xD;
             Philadelphia chromosome positive(Ph+) disease that are intolerant to or have failed 2&#xD;
             lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated&#xD;
             are eligible.&#xD;
&#xD;
          -  No salvage chemotherapy therapy within 4 weeks prior to C-CAR011 therapy.&#xD;
&#xD;
          -  No immunosuppressant(including but not limited to systemic corticosteroid therapy)&#xD;
             within 4 weeks prior to C-CAR011 therapy.&#xD;
&#xD;
          -  No antibody therapy within 4 weeks prior to C-CAR011 therapy.&#xD;
&#xD;
          -  Normal cardiac function confirmed by ECHO with left ventricular ejection fraction&#xD;
             (LVEF) ≧ 50%, no evidence of pericardial effusion and clinically significant&#xD;
             arrhythmias.&#xD;
&#xD;
          -  Baseline oxygen saturation ≧ 92% on room air and with normal pulmonary function, no&#xD;
             evidence of active lung infection.&#xD;
&#xD;
          -  No contraindications of peripheral blood apheresis.&#xD;
&#xD;
          -  Expected survival ≧ 3 months.&#xD;
&#xD;
          -  Eastern cooperative oncology group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of severe allergic disease or allergic to one or more drugs.&#xD;
&#xD;
          -  Any kind of these laboratory testing: serum total bilirubin≧1.5mg/dl, serum&#xD;
             albumin≦35g/L, ALT, AST≧2.5×ULN, serum creatinine≧2.0mg/dl, platelets≦50×109/L.&#xD;
&#xD;
          -  Extramedullary disease.&#xD;
&#xD;
          -  Relapsed disease after allogeneic hematopoietic stem cell transplantation.&#xD;
&#xD;
          -  Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic&#xD;
             myelogenous leukemia lymphoid blast crisis.&#xD;
&#xD;
          -  Subjects with concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome,&#xD;
             Shwachman-Diamond syndrome or any other known bone marrow failure syndrome.&#xD;
&#xD;
          -  Subjects with grade III or above severe hypertension(WHO/ISH Guidelines for the&#xD;
             Management of Hypertension, 1999).&#xD;
&#xD;
          -  History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or&#xD;
             other clinically significant cardiac disease within 12 months prior to enrollment.&#xD;
&#xD;
          -  Subjects with class III and IV heart failure according to the NYHA Heart Failure&#xD;
             Classifications;&#xD;
&#xD;
          -  History of QT prolongation with clinically significant arrhythmias.&#xD;
&#xD;
          -  History of epilepsy or other central nervous system disorders.&#xD;
&#xD;
          -  History or presence of any central nervous system leukemia(CNS3, CNS4) disorder , with&#xD;
             insensitive to intrathecal injection of or radiotherapy of head/spine; but effectively&#xD;
             controlled cases will be eligible.&#xD;
&#xD;
          -  Autoimmune diseases needing treatment, or immune deficiency or other diseases needing&#xD;
             immunosuppressive therapy.&#xD;
&#xD;
          -  Subjects with TKIs therapy (Ph+ ALL) within 1 week prior to enrollment.&#xD;
&#xD;
          -  Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis&#xD;
             allowed) or currently receiving intravenous antibiotic therapy and has received&#xD;
             intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and&#xD;
             antifungal treatment is permissible.&#xD;
&#xD;
          -  Used any genetically modified T cell therapy.&#xD;
&#xD;
          -  Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube,&#xD;
             indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter).&#xD;
             Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath&#xD;
             or Hickman catheter are permitted.&#xD;
&#xD;
          -  Live vaccine≦4 weeks prior to enrollment.&#xD;
&#xD;
          -  Known infection with HIV, TB, hepatitis B (including carriers) or hepatitis C virus&#xD;
             (anti-HCV positive).&#xD;
&#xD;
          -  History of alcohol addiction , drug abuse or mental disease.&#xD;
&#xD;
          -  Participated in any other clinical trial within three months prior to enrollment.&#xD;
&#xD;
          -  Women who are pregnant or lactating or have breeding intent within 6 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>14 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Li Yu</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese PLA General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Li Yu</last_name>
    <phone>010-66937644</phone>
    <email>liyu301@vip.163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chinese PLA General Hospital</name>
      <address>
        <city>Beijing Shi</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Yu</last_name>
      <phone>010-66937644</phone>
      <email>liyu301@vip.163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsed or refractory acute lymphoblastic leukemia</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>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/NCT03018093
org study id: CBMG2016003
nct id: NCT03018093
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 adult subjects with
      relapsed/refractory CD19+ B cells acute lymphoblastic leukemia(r/r CD19+B-ALL)
This is a single-center, Open Label phase I clinical trial, 20 subjects planned to be
      enrolled. The trial have two stages (Phase I dose-escalation clinical trial and phase I dose
      expansion trial).Subjects will be divided into low-dose group, medium-dose group and
      high-dose group.Additional patients will be enrolled to confirm the optimal dose

      Dose CAR+ cells/kg Low 0.5×106 Medium 1.5×106 High 3.0×106
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity (DLT)
time frame: 30 days
measure: Overall response rate (ORR)
time frame: 8 weeks
measure: Overall survival (OS)
time frame: 24 weeks
measure: Minimal residual disease negative remission rate(MRD-)
time frame: 8 weeks
arm group label: C-CAR011
arm group type: Experimental
description: In day 0, 1 and 2, CAR011 cells will be intravenous infused at the 10%, 30% and 60% ratio respectively.
intervention type: Biological
intervention name: C-CAR-011
description: CD19-targeted chimeric antigen receptor T cells
arm group label: C-CAR011
other name: CAR-CD19
criteria: 
gender: All
minimum age: 14 Years
maximum age: 75 Years
healthy volunteers: No
last name: Li Yu
role: Principal Investigator
affiliation: Chinese PLA General Hospital
last name: Li Yu
phone: 010-66937644
email: liyu301@vip.163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
sharing ipd: Undecided