<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/NCT04427449</url>
  </required_header>
  <id_info>
    <org_study_id>GIMI-IRB-20004</org_study_id>
    <nct_id>NCT04427449</nct_id>
  </id_info>
  <brief_title>4SCAR-CD44v6 T Cell Therapy Targeting Cancer</brief_title>
  <official_title>Multi-center Phase I/II Clinical Trial of 4SCAR-CD44v6 T Cells for Treating Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shenzhen Hospital of Southern Medical University</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>
    <collaborator>
      <agency>Shenzhen Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shenzhen Geno-Immune Medical Institute</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this clinical trial is to assess the feasibility, safety and efficacy of&#xD;
      4SCAR-CD44v6 T-cell therapy targeting multiple cancers. The study also aims to learn more&#xD;
      about the function of the CD44v6 CAR-T cells and their persistency in the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CD44 variant domain 6 (CD44v6) which belongs to CD44 family has been implicated in&#xD;
      tumorigenesis, tumor cell invasion and metastasis. The expression of CD44v6 was reported for&#xD;
      the majority of squamous cell carcinomas, a proportion of adenocarcinomas of differing&#xD;
      origin, a proportion of melanoma and lymphoma. This expression pattern has made CD44v6 an&#xD;
      attractive target for the therapy of various types of CD44v6 positive cancers.&#xD;
&#xD;
      The T cells from patients or transplantation donors will be genetically modified with&#xD;
      lentiviral CAR vector to recognize specific molecules - CD44v6 expressed on the surface of&#xD;
      the cancer cells. The engineered T cells will be applied to patients through intravenous&#xD;
      delivery.&#xD;
&#xD;
      The purpose of this clinical trial is to assess the feasibility, safety and efficacy of&#xD;
      CD44v6 CAR-T cell therapy in multiple cancers including - but not limited to - stomach&#xD;
      cancer, breast cancer, prostate cancer, multiple myeloma and lymphoma which are CD44v6&#xD;
      positive. Another goal of the study is to learn more about the function of the 4SCAR-CD44v6 T&#xD;
      cells and their persistency in the patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">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 infusion</measure>
    <time_frame>1 year</time_frame>
    <description>Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical response</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>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Cancers Which Are CD44v6 Positive</condition>
  <arm_group>
    <arm_group_label>Experimental: Single arm 4SCAR-CD44v6 T cells to treat cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CD44v6-specific CAR gene-engineered T cells</intervention_name>
    <description>4SCAR-CD44v6 Infusion of 4SCAR-CD44v6 T cells at 10^6 cells/kg body weight</description>
    <arm_group_label>Experimental: Single arm 4SCAR-CD44v6 T cells to treat cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age older than 6 months.&#xD;
&#xD;
          2. Confirmed expression of CD44v6 in tumor specimens by immuno-histochemical staining or&#xD;
             flow cytometry.&#xD;
&#xD;
          3. Karnofsky performance status (KPS) score is higher than 70 and life expectancy &gt; 3&#xD;
             months.&#xD;
&#xD;
          4. Adequate bone marrow, liver and renal function as assessed by the following laboratory&#xD;
             requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤&#xD;
             2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine&#xD;
             aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.&#xD;
&#xD;
          5. Hgb≥80g/L.&#xD;
&#xD;
          6. No cell separation contraindications.&#xD;
&#xD;
          7. Abilities to understand and the willingness to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Sever illness or medical condition, which would not permit the patient to be managed&#xD;
             according to the protocol, including active uncontrolled infection.&#xD;
&#xD;
          2. Active bacterial, fungal or viral infection not controlled by adequate treatment.&#xD;
&#xD;
          3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.&#xD;
&#xD;
          4. Pregnant or nursing women may not participate.&#xD;
&#xD;
          5. Use of glucocorticoid for systemic therapy within one week prior to entering the&#xD;
             trial.&#xD;
&#xD;
          6. Receive treatment related to CD44v6 targeted therapy.&#xD;
&#xD;
          7. Patients, in the opinion of investigators, may not be able to comply with the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <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>Xiuli Yuan, MD</last_name>
      <phone>86-18938690212</phone>
      <email>18938690212@163.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, PhD</last_name>
      <phone>86-075586725195</phone>
      <email>c@szgimi.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shenzhen Hospital of Southern Medical University</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <zip>518101</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jie Mao, MD</last_name>
      <phone>86-0755-233</phone>
      <email>myw921@163.com</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 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 9, 2020</last_update_submitted>
  <last_update_submitted_qc>June 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shenzhen Geno-Immune Medical Institute</investigator_affiliation>
    <investigator_full_name>Lung-Ji Chang</investigator_full_name>
    <investigator_title>President</investigator_title>
  </responsible_party>
  <keyword>CAR-T</keyword>
  <keyword>CD44v6</keyword>
  <keyword>Breast cancer</keyword>
  <keyword>Gastric cancer</keyword>
  <keyword>Lymphoma</keyword>
  <!-- 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/NCT04427449
org study id: GIMI-IRB-20004
nct id: NCT04427449
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this clinical trial is to assess the feasibility, safety and efficacy of
      4SCAR-CD44v6 T-cell therapy targeting multiple cancers. The study also aims to learn more
      about the function of the CD44v6 CAR-T cells and their persistency in the patients.
CD44 variant domain 6 (CD44v6) which belongs to CD44 family has been implicated in
      tumorigenesis, tumor cell invasion and metastasis. The expression of CD44v6 was reported for
      the majority of squamous cell carcinomas, a proportion of adenocarcinomas of differing
      origin, a proportion of melanoma and lymphoma. This expression pattern has made CD44v6 an
      attractive target for the therapy of various types of CD44v6 positive cancers.

      The T cells from patients or transplantation donors will be genetically modified with
      lentiviral CAR vector to recognize specific molecules - CD44v6 expressed on the surface of
      the cancer cells. The engineered T cells will be applied to patients through intravenous
      delivery.

      The purpose of this clinical trial is to assess the feasibility, safety and efficacy of
      CD44v6 CAR-T cell therapy in multiple cancers including - but not limited to - stomach
      cancer, breast cancer, prostate cancer, multiple myeloma and lymphoma which are CD44v6
      positive. Another goal of the study is to learn more about the function of the 4SCAR-CD44v6 T
      cells and their persistency in the patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of infusion
time frame: 1 year
description: Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.
measure: Clinical response
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: Experimental: Single arm 4SCAR-CD44v6 T cells to treat cancer
arm group type: Experimental
intervention type: Biological
intervention name: CD44v6-specific CAR gene-engineered T cells
description: 4SCAR-CD44v6 Infusion of 4SCAR-CD44v6 T cells at 10^6 cells/kg body weight
arm group label: Experimental: Single arm 4SCAR-CD44v6 T cells to treat cancer
criteria: 
gender: All
minimum age: 6 Months
maximum age: 75 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shenzhen Geno-Immune Medical Institute
investigator full name: Lung-Ji Chang
investigator title: President