<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/NCT04429438</url>
  </required_header>
  <id_info>
    <org_study_id>GIMI-IRB-20006</org_study_id>
    <nct_id>NCT04429438</nct_id>
  </id_info>
  <brief_title>Multi-CAR-T Cells Targeting B Cell Lymphomas</brief_title>
  <official_title>Primary, Booster and Consolidation Multi-CAR-T Cell Therapy for the Treatment of Refractory B Cell Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Seventh Affiliated Hospital of Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenzhen Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shenzhen Geno-Immune Medical Institute</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 safety and efficacy of a combination of 4th generation chimeric&#xD;
      antigen receptor gene-modified T cells targeting B cell surface molecules including CD19 and&#xD;
      alternative CARTs as booster and consolidation treatment for patients with highly resistant B&#xD;
      cell lymphomas, including primary mediastinal B cell lymphoma (PMBCL) and BCL involving&#xD;
      central nervous system (CNS-BCL). Clinical response and development of a simplified and&#xD;
      standardized lentiviral vector and cell production protocol will be investigated. This is a&#xD;
      phase I/II trial enrolling patients from multiple clinical centers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chimeric antigen receptor (CAR) T cell therapy has proven effective in treating B cell&#xD;
      malignancies. However, post CD19-CART relapses occur at high rate due to the CD19 antigen&#xD;
      loss or the exhaustion of CART cells. Furthermore, the success of treating&#xD;
      relapsed/refractory B cell lymphoma (BCL) such as primary mediastinal B-cell lymphoma (PMBCL)&#xD;
      and CNS-involved BCL has been limited. To overcome tumor escape and prolong in vivo CART&#xD;
      efficacy, we have developed a novel multiple CAR-T therapy regimen including booster and&#xD;
      consolidation CART applications to to target highly-refractory cancer. Selected patients will&#xD;
      be enrolled after target antigen confirmation including CD19, CD20, CD22, CD70, CD13, CD79b,&#xD;
      GD2 and PSMA through immunostaining of their tumor specimens. The aim is to evaluate safety&#xD;
      and long term efficacy of the multiple CART therapy strategy in the BCL patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</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 of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion</measure>
    <time_frame>24 weeks</time_frame>
    <description>Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells in patients with relapsed B cell lymphoma (BCL) using CTCAE 4 standard to evaluate the level of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti tumor activity of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion</measure>
    <time_frame>1 year</time_frame>
    <description>Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">11</enrollment>
  <condition>B Cell Lymphoma (BCL)</condition>
  <arm_group>
    <arm_group_label>4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have relapsed and refractory B cell lymphoma (BCL) after chemotherapy will be treated with a combination of 4SCAR gene-engineered T cells.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2</intervention_name>
    <description>Patients who have relapsed and refractory B cell lymphoma (BCL) after conventional chemotherapy will be treated with multiple 4SCAR gene-engineered T cells</description>
    <arm_group_label>4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age older than 6 months.&#xD;
&#xD;
          2. Primary B cell lymphoma surface expression of CD19 and/or CD22/CD70/PSMA/&#xD;
             CD13/CD79b/GD2 molecules.&#xD;
&#xD;
          3. The KPS score over 80 points, and survival time is more than 1 month.&#xD;
&#xD;
          4. Greater than Hgb 80 g/L.&#xD;
&#xD;
          5. No contraindications to blood cell collection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Accompanied with other active diseases, and difficult to assess response after&#xD;
             treatment.&#xD;
&#xD;
          2. Bacterial, fungal, or viral infection, unable to control.&#xD;
&#xD;
          3. Living with HIV.&#xD;
&#xD;
          4. Active HBV and HCV infection.&#xD;
&#xD;
          5. Pregnant and nursing mothers.6. under systemic steroid treatment within a week of the&#xD;
             treatment.&#xD;
&#xD;
        7. Prior failed CAR-T treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Lung-Ji Chang, Ph.D</last_name>
    <phone>+86-0755 8672-5195</phone>
    <email>c@szgimi.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shenzhen Children's Hospital</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sixi Liu, MD</last_name>
      <phone>86-189 3869 0206</phone>
      <email>tiger647@126.com</email>
    </contact>
    <contact_backup>
      <last_name>Lichun Xie, MD</last_name>
      <phone>86-19925192721</phone>
      <email>xielichunst@sina.com</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Shenzhen Geno-Immune Medical Institute</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lung-Ji Chang, Ph.D</last_name>
      <phone>+86-0755 8672-5195</phone>
      <email>c@szgimi.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Seventh Affilliated Hospital, Sun Yat-Sen University</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518107</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bo Wang, MD</last_name>
      <phone>86-0755-23242570</phone>
      <email>wangb68377@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>June 10, 2020</last_update_submitted>
  <last_update_submitted_qc>June 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CAR-T</keyword>
  <keyword>CD19</keyword>
  <keyword>CD20</keyword>
  <keyword>CD22</keyword>
  <keyword>CD70</keyword>
  <keyword>PSMA</keyword>
  <keyword>CD13</keyword>
  <keyword>CD79b</keyword>
  <keyword>GD2</keyword>
  <keyword>PMBCL</keyword>
  <keyword>CNS-BCL</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>
  </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/NCT04429438
org study id: GIMI-IRB-20006
nct id: NCT04429438
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate safety and efficacy of a combination of 4th generation chimeric
      antigen receptor gene-modified T cells targeting B cell surface molecules including CD19 and
      alternative CARTs as booster and consolidation treatment for patients with highly resistant B
      cell lymphomas, including primary mediastinal B cell lymphoma (PMBCL) and BCL involving
      central nervous system (CNS-BCL). Clinical response and development of a simplified and
      standardized lentiviral vector and cell production protocol will be investigated. This is a
      phase I/II trial enrolling patients from multiple clinical centers.
Chimeric antigen receptor (CAR) T cell therapy has proven effective in treating B cell
      malignancies. However, post CD19-CART relapses occur at high rate due to the CD19 antigen
      loss or the exhaustion of CART cells. Furthermore, the success of treating
      relapsed/refractory B cell lymphoma (BCL) such as primary mediastinal B-cell lymphoma (PMBCL)
      and CNS-involved BCL has been limited. To overcome tumor escape and prolong in vivo CART
      efficacy, we have developed a novel multiple CAR-T therapy regimen including booster and
      consolidation CART applications to to target highly-refractory cancer. Selected patients will
      be enrolled after target antigen confirmation including CD19, CD20, CD22, CD70, CD13, CD79b,
      GD2 and PSMA through immunostaining of their tumor specimens. The aim is to evaluate safety
      and long term efficacy of the multiple CART therapy strategy in the BCL patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion
time frame: 24 weeks
description: Safety of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells in patients with relapsed B cell lymphoma (BCL) using CTCAE 4 standard to evaluate the level of adverse events
measure: Anti tumor activity of fourth generation anti-CD19 and anti-CD20/CD22/CD70/PSMA/CD13/CD79b/GD2 CAR-T cells infusion
time frame: 1 year
description: Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
arm group label: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2
arm group type: Experimental
description: Patients who have relapsed and refractory B cell lymphoma (BCL) after chemotherapy will be treated with a combination of 4SCAR gene-engineered T cells.
intervention type: Biological
intervention name: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2
description: Patients who have relapsed and refractory B cell lymphoma (BCL) after conventional chemotherapy will be treated with multiple 4SCAR gene-engineered T cells
arm group label: 4SCAR19 and 4SCAR20/22/70/PSMA/13/79b/GD2
criteria: 
gender: All
minimum age: 6 Months
maximum age: 75 Years
healthy volunteers: No
last name: Lung-Ji Chang, Ph.D
phone: +86-0755 8672-5195
email: c@szgimi.org
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
sharing ipd: No