xml: <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/NCT05995028</url>
    </required_header>
    <id_info>
      <org_study_id>GIMI-IRB-23002</org_study_id>
      <nct_id>NCT05995028</nct_id>
    </id_info>
    <brief_title>Universal 4SCAR7U Targeting CD7-positive Malignancies</brief_title>
    <official_title>Safety and Efficacy of Universal 4SCAR7U T Cell Therapy Targeting CD7-positive Hematological Malignancies</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shenzhen Geno-Immune Medical Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Beijing Jingdu Children's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The Second Affiliated Hospital of Hainan Medical 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>
        The purpose of this clinical trial is to assess the feasibility, safety and efficacy of&#xD;
        universal CAR T cells based on 4SCAR7U design against CD7-positive hematological malignancies&#xD;
        using CD7 specific universal CAR T cells. The study also aims to learn more about the&#xD;
        function of CD7 targeting CAR T cells and their persistence in patients of hematological&#xD;
        malignancies.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hematological malignancies including B-, T-cell acute lymphoblastic leukemia (B-ALL, T-ALL),&#xD;
        B and T cell lymphoma (BCL, TCL), natural killer cell lymphoma (NKL) and acute myeloid&#xD;
        leukemia (AML) are aggressive diseases which may express the early T cell development&#xD;
        molecule CD7.T-ALL represents 15% of childhood and 25% of adult ALL, and T-ALL patients are&#xD;
        prone to early disease relapse and suffer from poor treatment outcomes. According to European&#xD;
        Group for the Immunological Characterization of Leukemias (EGIL), the presence of cytoplasmic&#xD;
        or membrane expression of CD3 defines T-ALL. Several immunophenotypic classifications have&#xD;
        been proposed: (TI) the immature subgroup or pro-T-ALL is defined by the expression of CD7&#xD;
        and cCD3; (TII) pre-T-ALL also expresses CD2 and/or CD5 and/or CD8; (TIII) or cortical T-ALL&#xD;
        shows CD1a positivity; and (TIV), mature T-ALL is characterized by the presence of surface&#xD;
        CD3 and CD1a negativity.Over the past few years, T cells modified with lentiviral chimeric&#xD;
        antigen receptor (CAR) gene have been studied in different clinical settings. CD7 is a T cell&#xD;
        surface molecule that plays important role in T cell and B cell interaction in early lymphoid&#xD;
        development, displays membrane expression early during T cell development before TCR&#xD;
        rearrangement, and persists through terminal stages of T cell development, and has been a&#xD;
        well-known marker for T-ALL. CD7 is considered a promising target for the treatment of T-ALL,&#xD;
        TCL, AML and NKL. In this study, the study proposes to investigate an universal CD7 targeting&#xD;
        CAR-T design, 4SCAR7U in combination with alternative targeting CAR-T cells as a new strategy&#xD;
        to treat CD7-positive hematological malignancies.&#xD;
  &#xD;
        The 4SCAR7U T cells are genetically engineered and manufactured in bulk amount that can be&#xD;
        supplied off-the-shelf without being custom made from individual patients. The immediate&#xD;
        availability of the CAR-T cells makes clinical treatment convenient and timely for rapid&#xD;
        progressing disease or for highly immune suppressed patients. This application can be time-&#xD;
        and cost-effective. This novel approach may also overcome problems of functionally defective&#xD;
        autologous T cells. The purpose of this clinical trial is to assess the feasibility, safety&#xD;
        and efficacy of the 4SCAR7U T cell product in hematological malignancies. Another goal of the&#xD;
        study is to learn more about the function of this novel product and its persistence in the&#xD;
        patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2026</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 of infusion</measure>
      <time_frame>6 months</time_frame>
      <description>Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.</description>
    </primary_outcome>
    <secondary_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>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>T-cell Acute Lymphoblastic Leukemia</condition>
    <condition>T-cell Acute Lymphoblastic Lymphoma</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>NK Cell Lymphoma</condition>
    <arm_group>
      <arm_group_label>Universal 4SCAR7U cells to treat CD7-positive hematological malignancies</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Universal CD7-specific CAR gene-engineered T cells</intervention_name>
      <description>Infusion of 4SCAR7U T cells</description>
      <arm_group_label>Universal 4SCAR7U cells to treat CD7-positive hematological malignancies</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age older than 6 months.&#xD;
  &#xD;
            2. Confirmed expression of CD7 and additional surface antigens in the cancer cells by&#xD;
               immuno-histochemical staining or flow cytometry.&#xD;
  &#xD;
            3. Karnofsky performance status (KPS) score is higher than 80 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 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. Previous treatment with any gene therapy products.&#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>
    <overall_contact>
      <last_name>Lung-Ji Chang, Ph.D</last_name>
      <phone>86-136 7112 1909</phone>
      <email>c@szgimi.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ying Deng</last_name>
      <phone>86-0755-8672 5195</phone>
      <email>c@szgimi.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Beijing Jingdu Children's Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Juan Xiao, PhD,MD</last_name>
        <phone>86-15801071228</phone>
        <email>15801071228@163.com</email>
      </contact>
    </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 Second Affiliated Hospital of Hainan Medical University</name>
        <address>
          <city>Haikou</city>
          <state>Hainan</state>
          <zip>570100</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Min Dong, PhD MD</last_name>
        <phone>86-189 7608 3736</phone>
        <email>mingdonghn@hainmc.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>T-ALL</keyword>
    <keyword>TCL</keyword>
    <keyword>AML</keyword>
    <keyword>NK lymphoma</keyword>
    <keyword>Universal CAR T</keyword>
    <keyword>CD7</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
      <mesh_term>Precursor T-Cell Lymphoblastic Leukemia-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>
  
  
text: 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/NCT05995028
  org study id: GIMI-IRB-23002
  nct id: NCT05995028
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  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
        universal CAR T cells based on 4SCAR7U design against CD7-positive hematological malignancies
        using CD7 specific universal CAR T cells. The study also aims to learn more about the
        function of CD7 targeting CAR T cells and their persistence in patients of hematological
        malignancies.
  Hematological malignancies including B-, T-cell acute lymphoblastic leukemia (B-ALL, T-ALL),
        B and T cell lymphoma (BCL, TCL), natural killer cell lymphoma (NKL) and acute myeloid
        leukemia (AML) are aggressive diseases which may express the early T cell development
        molecule CD7.T-ALL represents 15% of childhood and 25% of adult ALL, and T-ALL patients are
        prone to early disease relapse and suffer from poor treatment outcomes. According to European
        Group for the Immunological Characterization of Leukemias (EGIL), the presence of cytoplasmic
        or membrane expression of CD3 defines T-ALL. Several immunophenotypic classifications have
        been proposed: (TI) the immature subgroup or pro-T-ALL is defined by the expression of CD7
        and cCD3; (TII) pre-T-ALL also expresses CD2 and/or CD5 and/or CD8; (TIII) or cortical T-ALL
        shows CD1a positivity; and (TIV), mature T-ALL is characterized by the presence of surface
        CD3 and CD1a negativity.Over the past few years, T cells modified with lentiviral chimeric
        antigen receptor (CAR) gene have been studied in different clinical settings. CD7 is a T cell
        surface molecule that plays important role in T cell and B cell interaction in early lymphoid
        development, displays membrane expression early during T cell development before TCR
        rearrangement, and persists through terminal stages of T cell development, and has been a
        well-known marker for T-ALL. CD7 is considered a promising target for the treatment of T-ALL,
        TCL, AML and NKL. In this study, the study proposes to investigate an universal CD7 targeting
        CAR-T design, 4SCAR7U in combination with alternative targeting CAR-T cells as a new strategy
        to treat CD7-positive hematological malignancies.
  
        The 4SCAR7U T cells are genetically engineered and manufactured in bulk amount that can be
        supplied off-the-shelf without being custom made from individual patients. The immediate
        availability of the CAR-T cells makes clinical treatment convenient and timely for rapid
        progressing disease or for highly immune suppressed patients. This application can be time-
        and cost-effective. This novel approach may also overcome problems of functionally defective
        autologous T cells. The purpose of this clinical trial is to assess the feasibility, safety
        and efficacy of the 4SCAR7U T cell product in hematological malignancies. Another goal of the
        study is to learn more about the function of this novel product and its persistence in the
        patients.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety of infusion
  time frame: 6 months
  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: Universal 4SCAR7U cells to treat CD7-positive hematological malignancies
  arm group type: Experimental
  intervention type: Biological
  intervention name: Universal CD7-specific CAR gene-engineered T cells
  description: Infusion of 4SCAR7U T cells
  arm group label: Universal 4SCAR7U cells to treat CD7-positive hematological malignancies
  criteria: 
  gender: All
  minimum age: 6 Months
  maximum age: 75 Years
  healthy volunteers: No
  last name: Lung-Ji Chang, Ph.D
  phone: 86-136 7112 1909
  email: c@szgimi.org
  last name: Ying Deng
  phone: 86-0755-8672 5195
  email: c@szgimi.org
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Leukemia
  mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  mesh term: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
  sharing ipd: No