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/NCT05995041</url>
    </required_header>
    <id_info>
      <org_study_id>GIMI-IRB-23004</org_study_id>
      <nct_id>NCT05995041</nct_id>
    </id_info>
    <brief_title>Universal CAR-T Cells Targeting AML</brief_title>
    <official_title>Universal CAR T Cells for the Treatment of Acute Myeloid Leukemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shenzhen Geno-Immune Medical Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The Second Affiliated Hospital of Hainan Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Beijing Jingdu 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>
        The purpose of this clinical trial is to assess the feasibility, safety and efficacy of&#xD;
        universal CAR T-cell products targeting CLL-1, CD33, CD38 and CD123 in patients with relapsed&#xD;
        and refractory AML. The study also aims to learn more about the function of the universal CAR&#xD;
        T cells and their persistency in AML patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Acute myeloid leukemia (AML) is a malignant disease characterized by the rapid growth of&#xD;
        myeloblasts that grow in the bone marrow and interferes with the generation of normal blood&#xD;
        cells.Over the past years, several groups have demonstrated that CLL1, CD33, CD38 and CD123&#xD;
        are potential AML targets. CLL-1 (C-type lectin-like molecule-1) is a transmembrane&#xD;
        glycoprotein, which is overexpressed in leukemic stem cells but absent in normal&#xD;
        hematopoietic stem cells, suggesting that CLL-1 can be a promising target for targeted AML&#xD;
        therapy. Although CAR-T cells have shown impressive anti-leukemic effect in B cell disease,&#xD;
        CAR-T treatment for AML has proven to be more difficult. One of the reasons is because AML&#xD;
        patients often has highly suppressed bone marrow function, and it is often difficult to&#xD;
        obtain good quality of T cells for CAR-T preparation. In addition, AML progression can be&#xD;
        acute and rapid, which can outpace the CAR-T expansion, and the time-consuming CAR-T&#xD;
        manufacture process makes it more difficult to treat AML with autologous source of T cells By&#xD;
        using universal type of CAR-T cells, the product can be supplied off-the-shelf without being&#xD;
        customized from individual patients. In addition, the immediate availability means that&#xD;
        patients with short disease remission time under severe bone marrow suppression may get a&#xD;
        chance to be treated with CAR-T cells to achieve disease remission. In addition, those&#xD;
        patients who suffer from long-term immunosuppression due to tumor microenvironment or&#xD;
        myelosuppressive chemotherapy would have the option of treatment with the universal CAR-T&#xD;
        cells.&#xD;
  &#xD;
        The purpose of this study is to assess the feasibility, safety and efficacy of several&#xD;
        AML-specific universal CAR-T products. Another goal is to learn more about the function of&#xD;
        the universal CAR T cells and their persistency in the patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 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>Acute Myeloid Leukemia</condition>
    <arm_group>
      <arm_group_label>Multiple universal CAR T cells to treat AML</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>CLL-1, CD33, CD38 and/or CD123-specific universal CAR- T cells</intervention_name>
      <description>Infusion of CLL-1, CD33, CD38 and/or CD123-specific universal CAR- T cells</description>
      <arm_group_label>Multiple universal CAR T cells to treat AML</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age older than 6 months.&#xD;
  &#xD;
            2. Confirmed expression of CLL-1, CD123, CD38 and/or CD33 in AML blasts 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 active 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. The bone marrow AML burden (MRD) is above 50%.&#xD;
  &#xD;
            8. 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>86-0755-8672 5195</phone>
      <email>c@szgimi.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ying Deng</last_name>
      <phone>86-0755-8672 5195</phone>
      <email>ying.deng@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 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>AML</keyword>
    <keyword>Universal CAR T</keyword>
    <keyword>CD33, CD123, CD38, CLL-1</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</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/NCT05995041
  org study id: GIMI-IRB-23004
  nct id: NCT05995041
  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-cell products targeting CLL-1, CD33, CD38 and CD123 in patients with relapsed
        and refractory AML. The study also aims to learn more about the function of the universal CAR
        T cells and their persistency in AML patients.
  Acute myeloid leukemia (AML) is a malignant disease characterized by the rapid growth of
        myeloblasts that grow in the bone marrow and interferes with the generation of normal blood
        cells.Over the past years, several groups have demonstrated that CLL1, CD33, CD38 and CD123
        are potential AML targets. CLL-1 (C-type lectin-like molecule-1) is a transmembrane
        glycoprotein, which is overexpressed in leukemic stem cells but absent in normal
        hematopoietic stem cells, suggesting that CLL-1 can be a promising target for targeted AML
        therapy. Although CAR-T cells have shown impressive anti-leukemic effect in B cell disease,
        CAR-T treatment for AML has proven to be more difficult. One of the reasons is because AML
        patients often has highly suppressed bone marrow function, and it is often difficult to
        obtain good quality of T cells for CAR-T preparation. In addition, AML progression can be
        acute and rapid, which can outpace the CAR-T expansion, and the time-consuming CAR-T
        manufacture process makes it more difficult to treat AML with autologous source of T cells By
        using universal type of CAR-T cells, the product can be supplied off-the-shelf without being
        customized from individual patients. In addition, the immediate availability means that
        patients with short disease remission time under severe bone marrow suppression may get a
        chance to be treated with CAR-T cells to achieve disease remission. In addition, those
        patients who suffer from long-term immunosuppression due to tumor microenvironment or
        myelosuppressive chemotherapy would have the option of treatment with the universal CAR-T
        cells.
  
        The purpose of this study is to assess the feasibility, safety and efficacy of several
        AML-specific universal CAR-T products. Another goal is to learn more about the function of
        the universal CAR 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: 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: Multiple universal CAR T cells to treat AML
  arm group type: Experimental
  intervention type: Biological
  intervention name: CLL-1, CD33, CD38 and/or CD123-specific universal CAR- T cells
  description: Infusion of CLL-1, CD33, CD38 and/or CD123-specific universal CAR- T cells
  arm group label: Multiple universal CAR T cells to treat AML
  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
  last name: Ying Deng
  phone: 86-0755-8672 5195
  email: ying.deng@szgimi.org
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute
  sharing ipd: No