<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/NCT04430530</url>
  </required_header>
  <id_info>
    <org_study_id>GIMI-IRB-20008</org_study_id>
    <nct_id>NCT04430530</nct_id>
  </id_info>
  <brief_title>4SCAR-T Therapy Post CD19-targeted Immunotherapy</brief_title>
  <official_title>4SCAR-T Therapy After Anti-CD19 Immunotherapy Targeting B Cell Acute Lymphoblastic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ShiJiaZhuang Zhongxi Children Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shenzhen Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Seventh Affiliated Hospital of Sun Yat-sen University</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 will evaluate safety and efficacy of a combination of 4th generation chimeric&#xD;
      antigen receptor gene-modified T cells (4SCAR-T) targeting CD19-negative B-ALL that express&#xD;
      alternative surface antigens such as CD22, CD10, CD20, CD38, and CD123, as many patients&#xD;
      relapse after anti-CD19 immunotherapy. Clinical response and optiminzation of a standardized&#xD;
      lentiviral vector and cell production protocol will be investigated. This is a phase I/II&#xD;
      trial enrolling patients from multiple clinical centers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anti-CD19 immunotherapy based on antibody conjugated drugs or CD19-CAR-T cells has&#xD;
      demonstrated unprecedented positive response in relapsing/refractory B-cell acute&#xD;
      lymphoblastic leukemia (r/r B-ALL). However, many patients still relapse and up to 30-50% of&#xD;
      those relapses are characterized by the loss of CD19 surface antigen. Patients with&#xD;
      CD19-negative relapse usually have a poor prognosis. The mechanisms underlying CD19-negative&#xD;
      relapses are not fully understood and it is important to develop solutions to supplement&#xD;
      post-CD19 immunotherapies.&#xD;
&#xD;
      Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population&#xD;
      include many known B-cell lineage antigens. To prevent further target escape and improve the&#xD;
      therapeutic effects, the 4th generation CAR gene-modified T cells targeting CD22, CD10, CD20,&#xD;
      CD38, or CD123 have been considered in post anti-CD19 treatment. This study aims to evaluate&#xD;
      safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to&#xD;
      patients with CD19-escaped B cell malignancies.&#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">May 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-CD22/CD123/CD38/CD10/CD20 CAR-T cells</measure>
    <time_frame>24 weeks</time_frame>
    <description>Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells</measure>
    <time_frame>1 year</time_frame>
    <description>Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>CD19 Negative B-cell Malignancies</condition>
  <arm_group>
    <arm_group_label>4SCAR-CD22/CD123/CD38/CD10/CD20 infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20</intervention_name>
    <description>Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies</description>
    <arm_group_label>4SCAR-CD22/CD123/CD38/CD10/CD20 infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age older than 6 months.&#xD;
&#xD;
          2. B cell malignancies relapsed after anti-CD19 immunotherapy.&#xD;
&#xD;
          3. Malignant B cells expressing one or more of the following surface molecules:&#xD;
             CD22/CD123/CD38/CD10/CD20.&#xD;
&#xD;
          4. The KPS score over 80 points, and survival time is more than 1 month.&#xD;
&#xD;
          5. Greater than Hgb 80 g/L.&#xD;
&#xD;
          6. No contraindications to blood cell collection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Complications with other active diseases, and difficult to assess patient response.&#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.&#xD;
&#xD;
          6. Under systemic steroid use within a week of the treatment.&#xD;
&#xD;
          7. Judged difficult to cooporate for continued evaluation.&#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, phD</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>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>
    <facility>
      <name>Shijiazhuang Zhongxi Children Hospital</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guangming Qiao, MD</last_name>
      <phone>+86-13731113069</phone>
    </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>4S CAR-T CD22</keyword>
  <keyword>4S CAR-T CD123</keyword>
  <keyword>4S CAR-T CD38</keyword>
  <keyword>4S CAR-T CD10</keyword>
  <keyword>4S CAR-T CD20</keyword>
  <keyword>CD19 Negative B cell leukemiaB-ALL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</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/NCT04430530
org study id: GIMI-IRB-20008
nct id: NCT04430530
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate safety and efficacy of a combination of 4th generation chimeric
      antigen receptor gene-modified T cells (4SCAR-T) targeting CD19-negative B-ALL that express
      alternative surface antigens such as CD22, CD10, CD20, CD38, and CD123, as many patients
      relapse after anti-CD19 immunotherapy. Clinical response and optiminzation of a standardized
      lentiviral vector and cell production protocol will be investigated. This is a phase I/II
      trial enrolling patients from multiple clinical centers.
Anti-CD19 immunotherapy based on antibody conjugated drugs or CD19-CAR-T cells has
      demonstrated unprecedented positive response in relapsing/refractory B-cell acute
      lymphoblastic leukemia (r/r B-ALL). However, many patients still relapse and up to 30-50% of
      those relapses are characterized by the loss of CD19 surface antigen. Patients with
      CD19-negative relapse usually have a poor prognosis. The mechanisms underlying CD19-negative
      relapses are not fully understood and it is important to develop solutions to supplement
      post-CD19 immunotherapies.

      Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population
      include many known B-cell lineage antigens. To prevent further target escape and improve the
      therapeutic effects, the 4th generation CAR gene-modified T cells targeting CD22, CD10, CD20,
      CD38, or CD123 have been considered in post anti-CD19 treatment. This study aims to evaluate
      safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to
      patients with CD19-escaped B cell malignancies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells
time frame: 24 weeks
description: Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.
measure: Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells
time frame: 1 year
description: Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry
arm group label: 4SCAR-CD22/CD123/CD38/CD10/CD20 infusion
arm group type: Experimental
description: Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies
intervention type: Biological
intervention name: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20
description: Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies
arm group label: 4SCAR-CD22/CD123/CD38/CD10/CD20 infusion
criteria: 
gender: All
minimum age: 6 Months
maximum age: 75 Years
healthy volunteers: No
last name: Lung-Ji Chang, phD
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: Neoplasms
sharing ipd: No