<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/NCT03271515</url>
  </required_header>
  <id_info>
    <org_study_id>Doing-006</org_study_id>
    <nct_id>NCT03271515</nct_id>
  </id_info>
  <brief_title>Immunotherapy With Bispecific CAR-T Cells for B-Cell Lymphoma, ALL and CLL</brief_title>
  <official_title>Phase I Study of T Cells Expressing an Anti-CD19 and Anti-CD20 Bispecific Chimeric Receptor in Patients With B Cell Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Doing Biomedical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Doing Biomedical Co., Ltd.</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>
      This study aims to evaluate the safety, efficacy and duration of response of anti-CD19&#xD;
      anti-CD20 Bispecific Chimeric Antigen Receptor (CAR) redirected autologous T-cells in&#xD;
      patients with high risk, relapsed CD19+ and CD20+ haematological malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced&#xD;
      Therapy Investigational Medicinal Product named CD19 CD20 Chimeric Antigen Receptor (CAR)&#xD;
      T-cells (CD19 CAR T-cells) in patients with high risk, relapsed CD19+ and CD20+haematological&#xD;
      malignancies (Leukemia and lymphoma). Following informed consent and registration to the&#xD;
      trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19&#xD;
      CD20 CAR T-cells. Patients will receive the CD19 CD20 CAR T-cells following lymphodepleting&#xD;
      chemotherapy. The study will evaluate the safety, efficacy and duration of response of the&#xD;
      CD19 CD20 CAR T-cells in patients with high risk relapsed CD19+ malignancies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 1, 2021</start_date>
  <completion_date type="Anticipated">March 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Antitumor Effects</measure>
    <time_frame>Every 3 months post treatment up to 24 months</time_frame>
    <description>Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival time of Anti-CD19 Anti-CD20 CAR T cells in vivo.</measure>
    <time_frame>3 years</time_frame>
    <description>To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events of each patient.</measure>
    <time_frame>3 years</time_frame>
    <description>Determine the toxicity profile of the CD19 CD20 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Leukemia</condition>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>conventional therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>patients accept conventional radioactive and chemical therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>anti-CD19 anti-CD20 Bispecific CAR-T</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients accept transfusion of anti-CD19 anti-CD20 Bispecific CAR-T cells.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>anti-CD19 anti-CD20 Bispecific CAR-T</intervention_name>
    <description>patients accept transfusion of anti-CD19 anti-CD20 Bispecific CAR-T cells.</description>
    <arm_group_label>anti-CD19 anti-CD20 Bispecific CAR-T</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic&#xD;
             lymphoblastic leukemia(CLL) and non-hodgkin lymphoma.&#xD;
&#xD;
          2. KPS&gt;60.&#xD;
&#xD;
          3. Life expectancy&gt;3 months.&#xD;
&#xD;
          4. Gender unlimited, age from 18 years to 70 years.&#xD;
&#xD;
          5. CD19 or CD20 expression must be detected on greater than 15% of the malignant cells by&#xD;
             immunohistochemistry or greater than 30% by flow cytometry.&#xD;
&#xD;
          6. Patients who have failed at least one line of a standard treatment.&#xD;
&#xD;
          7. No serious mental disorder.&#xD;
&#xD;
          8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate&#xD;
             pulmonary function as indicated by room air oxygen saturation of &gt;94%, and adequate&#xD;
             renal function(Cr≤133umol/L).&#xD;
&#xD;
          9. No other serious diseases(autoimmune disease, immunodeficiency etc.).&#xD;
&#xD;
         10. No other tumors.&#xD;
&#xD;
         11. Patients volunteer to participate in the research.&#xD;
&#xD;
         12. Patients with history of allogeneic stem cell transplantation are eligible if at least&#xD;
             100 days post-transplant, if there is no evidence of active GVHD and no longer taking&#xD;
             immunosuppressive agents for at least 30 days prior to trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. KPS&lt;50.&#xD;
&#xD;
          2. Patients are allergic to cytokines.&#xD;
&#xD;
          3. Central nervous system leukemia within 28 days.&#xD;
&#xD;
          4. Uncontrolled active infection.&#xD;
&#xD;
          5. Acute or chronic GVHD.&#xD;
&#xD;
          6. Treated with T cell inhibitor.&#xD;
&#xD;
          7. Pregnancy and nursing females.&#xD;
&#xD;
          8. HIV/HBV/HCV Infection.&#xD;
&#xD;
          9. Other situations we think improper for the research.&#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>li gangyi</last_name>
    <role>Study Chair</role>
    <affiliation>Beijing Doing Biomedical Co., Ltd.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>gai liyun</last_name>
    <phone>086-13269099630</phone>
    <email>liyun_gai@doingtimes.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>li gangyi</last_name>
    <phone>086-13901106501</phone>
    <email>gangyi_li@doingtimes.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hebei Yanda Ludaopei Hospital</name>
      <address>
        <city>Sanhe</city>
        <state>Hebei</state>
        <zip>065200</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Gai liyun, Docter</last_name>
      <phone>086-13269099630</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>January 19, 2021</last_update_submitted>
  <last_update_submitted_qc>January 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>leukemia</keyword>
  <keyword>lymphoma</keyword>
  <keyword>CAR-T</keyword>
  <keyword>bispecific</keyword>
  <keyword>CD20</keyword>
  <keyword>CD19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03271515
org study id: Doing-006
nct id: NCT03271515
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate the safety, efficacy and duration of response of anti-CD19
      anti-CD20 Bispecific Chimeric Antigen Receptor (CAR) redirected autologous T-cells in
      patients with high risk, relapsed CD19+ and CD20+ haematological malignancies.
This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced
      Therapy Investigational Medicinal Product named CD19 CD20 Chimeric Antigen Receptor (CAR)
      T-cells (CD19 CAR T-cells) in patients with high risk, relapsed CD19+ and CD20+haematological
      malignancies (Leukemia and lymphoma). Following informed consent and registration to the
      trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19
      CD20 CAR T-cells. Patients will receive the CD19 CD20 CAR T-cells following lymphodepleting
      chemotherapy. The study will evaluate the safety, efficacy and duration of response of the
      CD19 CD20 CAR T-cells in patients with high risk relapsed CD19+ malignancies.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Antitumor Effects
time frame: Every 3 months post treatment up to 24 months
description: Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
measure: Survival time of Anti-CD19 Anti-CD20 CAR T cells in vivo.
time frame: 3 years
description: To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.
measure: Adverse events of each patient.
time frame: 3 years
description: Determine the toxicity profile of the CD19 CD20 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
arm group label: conventional therapy
arm group type: No Intervention
description: patients accept conventional radioactive and chemical therapy.
arm group label: anti-CD19 anti-CD20 Bispecific CAR-T
arm group type: Experimental
description: patients accept transfusion of anti-CD19 anti-CD20 Bispecific CAR-T cells.
intervention type: Biological
intervention name: anti-CD19 anti-CD20 Bispecific CAR-T
description: patients accept transfusion of anti-CD19 anti-CD20 Bispecific CAR-T cells.
arm group label: anti-CD19 anti-CD20 Bispecific CAR-T
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: li gangyi
role: Study Chair
affiliation: Beijing Doing Biomedical Co., Ltd.
last name: gai liyun
phone: 086-13269099630
email: liyun_gai@doingtimes.com
last name: li gangyi
phone: 086-13901106501
email: gangyi_li@doingtimes.com
facility: 
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
sharing ipd: No