<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/NCT03751293</url>
  </required_header>
  <id_info>
    <org_study_id>0203-006</org_study_id>
    <nct_id>NCT03751293</nct_id>
  </id_info>
  <brief_title>A Study of BCMA-directed CAR-T Cells Treatment in Subjects With r/r Multiple Myeloma</brief_title>
  <official_title>A Phase Ⅰ Study Evaluating Safety and Efficacy of C-CAR088 Treatment in Subjects With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hebei Yanda Ludaopei Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hebei Yanda Ludaopei Hospital</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-center, non-randomized study to evaluate the safety and efficacy of C-CAR088&#xD;
      in relapsed or refractory multiple myeloma patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will include the following sequential phases: Screening, Pre-Treatment (Cell&#xD;
      Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 8, 2019</start_date>
  <completion_date type="Anticipated">October 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2019</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: The incidence of treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>30 days</time_frame>
    <description>The incidence of treatment-emergent adverse events (TEAEs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>6 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The CART cell duration in vivo</measure>
    <time_frame>12 months</time_frame>
    <description>The copys of BCMA-CART DNA in peripheral blood with qPCR method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The soluble BCMA changes in peripheral blood</measure>
    <time_frame>12 months</time_frame>
    <description>The amount of soluble BCMA in peripheral blood with ELISA method</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Relapsed or Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>C-CAR088</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lymphocytes will be transduced with lentiviral vector containing CAR-BCMA gene</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>C-CAR088</intervention_name>
    <description>Autologous BCMA-directed CAR-T cells, single infusion intravenously at a target dose of 1.0-9.0 x 10^6 anti-BCMA CAR+ T cells/kg</description>
    <arm_group_label>C-CAR088</arm_group_label>
    <other_name>CBM.BCMA 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. Meet the internationally accepted Criteria for the diagnosis of multiple myeloma (IMWG&#xD;
             diagnostic criteria 2014).&#xD;
&#xD;
          4. Patients with relapsed or refractory multiple myeloma who meet at least one of the&#xD;
             following conditions:&#xD;
&#xD;
               -  Subjects must have received at least two therapy regimens (including proteasome&#xD;
                  inhibitor or immune-modulator therapy, disease progress or relapse after the last&#xD;
                  therapy).&#xD;
&#xD;
               -  Subjects have received only one therapy regimen, but the investigators judge that&#xD;
                  patients have unmet treatment needs or can't get benefit from current treatment&#xD;
                  options.&#xD;
&#xD;
          5. Subjects have one or more measurable multiple myeloma lesion, must include one of the&#xD;
             following conditions:&#xD;
&#xD;
               -  Serum M protein≥1 g/dl(10g/L)&#xD;
&#xD;
               -  Urine M protein≥200 mg/24h&#xD;
&#xD;
               -  Serum free light chain(sFLC): κ/λ ratio abnormal and ≥10 mg/dl&#xD;
&#xD;
          6. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological&#xD;
             examination.&#xD;
&#xD;
          7. At least 2 weeks from monoclonal antibody therapy prior to CAR T cell therapy.&#xD;
&#xD;
          8. ECOG scores 0 - 1.&#xD;
&#xD;
          9. Normal cardiac diastolic function, left ventricular ejection fraction (LVEF) ≥ 50%&#xD;
             (detected by echocardiography), no serious arrhythmia.&#xD;
&#xD;
         10. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92%&#xD;
             on room air.&#xD;
&#xD;
         11. No contraindications of leukapheresis.&#xD;
&#xD;
         12. Expected survival &gt; 12 weeks.&#xD;
&#xD;
         13. Female subjects in childbearing age, their serum or urine pregnancy test must be&#xD;
             negative,until 7 days before cell therapy and all subjects must agree to take&#xD;
             effective contraceptive measures during the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have a history of allergy to cellular products.&#xD;
&#xD;
          2. Any kind of these laboratory testing: including but not limited to,serum total&#xD;
             bilirubin≧1.5mg/dl, serum ALT, AST≧2.5×ULN, serum creatinine≧2.0mg/dl, Hb&#xD;
             (hemoglobin)&lt;80g/L, neutrophils&lt;1000/mm^3, platelets≦50000/mm^3 or platelet count&#xD;
             maintained by transfusion.&#xD;
&#xD;
          3. Subjects with the following clinically significant cardiovascular diseases.&#xD;
&#xD;
          4. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral&#xD;
             ischemia or hemorrhagic disease.&#xD;
&#xD;
          5. Use any anticoagulant (except aspirin).&#xD;
&#xD;
          6. Patients requiring urgent treatment due to tumor progression or spinal cord&#xD;
             compression.&#xD;
&#xD;
          7. Patients with CNS metastasis or symptoms of CNS involvement.&#xD;
&#xD;
          8. The investigators judge that any increase in the risk of the subject or interference&#xD;
             with the results of the trial.&#xD;
&#xD;
          9. After allogeneic hematopoietic stem cell transplantation.&#xD;
&#xD;
         10. Plasma cell leukemia.&#xD;
&#xD;
         11. One week before leukapheresis and one week before CART cell infusion, treated with&#xD;
             more than 5mg/d prednisone (or equal amount of other corticosteroids).&#xD;
&#xD;
         12. Subjects with any autoimmune disease or any immune deficiency disease or other disease&#xD;
             in need of immunosuppressive therapy.&#xD;
&#xD;
         13. Uncontrolled active infection.&#xD;
&#xD;
         14. Prior treatment with CAR T therapy or any other genetically modified T cell therapy.&#xD;
&#xD;
         15. Live vaccine inoculation within four weeks before enrollment.&#xD;
&#xD;
         16. Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as&#xD;
             acquired, congenital immune deficiency diseases, including but not limited to&#xD;
             HIV-infected persons.&#xD;
&#xD;
         17. Have a history of alcoholism, drug addiction and mental illness.&#xD;
&#xD;
         18. Participated in any other clinical trial within three months.&#xD;
&#xD;
         19. The investigators believe that there are other circumstances that are not suitable for&#xD;
             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_contact>
    <last_name>Peihua Lu, PhD&amp;MD</last_name>
    <phone>+86-0316-3306393</phone>
    <email>peihua_lu@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hebei Yanda Ludaopei Hospital</name>
      <address>
        <city>Sanhe</city>
        <state>Hebei</state>
        <zip>065200</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peihua Lu, PhD&amp;MD</last_name>
      <phone>+86-0316-3306393</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>May 13, 2019</last_update_submitted>
  <last_update_submitted_qc>May 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2019</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>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/NCT03751293
org study id: 0203-006
nct id: NCT03751293
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single-center, non-randomized study to evaluate the safety and efficacy of C-CAR088
      in relapsed or refractory multiple myeloma patient.
The study will include the following sequential phases: Screening, Pre-Treatment (Cell
      Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: The incidence of treatment-emergent adverse events (TEAEs)
time frame: 30 days
description: The incidence of treatment-emergent adverse events (TEAEs)
measure: Overall response rate (ORR)
time frame: 12 months
measure: Progression free survival (PFS)
time frame: 6 months, 12 months
measure: The CART cell duration in vivo
time frame: 12 months
description: The copys of BCMA-CART DNA in peripheral blood with qPCR method
measure: The soluble BCMA changes in peripheral blood
time frame: 12 months
description: The amount of soluble BCMA in peripheral blood with ELISA method
arm group label: C-CAR088
arm group type: Experimental
description: Lymphocytes will be transduced with lentiviral vector containing CAR-BCMA gene
intervention type: Biological
intervention name: C-CAR088
description: Autologous BCMA-directed CAR-T cells, single infusion intravenously at a target dose of 1.0-9.0 x 10^6 anti-BCMA CAR+ T cells/kg
arm group label: C-CAR088
other name: CBM.BCMA Chimeric Antigen Receptor T cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Peihua Lu, PhD&MD
phone: +86-0316-3306393
email: peihua_lu@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell