<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/NCT04429451</url>
  </required_header>
  <id_info>
    <org_study_id>GIMI-IRB-20003</org_study_id>
    <nct_id>NCT04429451</nct_id>
  </id_info>
  <brief_title>PSMA-specific CAR-T Cell Therapy</brief_title>
  <official_title>Phase I/II Clinical Trial of 4SCAR-PSMA T Cell Therapy Targeting PSMA Positive Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <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>
    <collaborator>
      <agency>Shenzhen Hospital of Southern Medical University</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;
      PSMA-specific CAR-T cell therapy in patients with PSMA positive tumor. Another goal of the&#xD;
      study is to learn more about the function of the PSMA CAR-T cells and their persistency in&#xD;
      the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prostate-specific membrane antigen (PSMA) is expressed in normal prostate and is upregulated&#xD;
      in prostate tumor. Therefore, PSMA is a promising target for antigen-specific immunotherapy&#xD;
      in patients with prostate cancer. However, it has been reported that PSMA expression is not&#xD;
      restricted to prostate cancer and PSMA is often enriched in the tumor stromal environment. By&#xD;
      immunostaining, we found that PSMA is expressed in a variety of solid tumors, including brain&#xD;
      tumor, neuroblastoma and some lymphoma tumor tissues.&#xD;
&#xD;
      This study aims to use T cells obtained directly from the patient, which can be genetically&#xD;
      modified to express PSMA-specific chimeric antigen receptor (CAR). The CAR molecules enable&#xD;
      the T cells to recognize and kill tumor cells or tumor stromal tissues through the&#xD;
      recognition of a surface antigen, PSMA. This study will evaluate the side effects and the&#xD;
      best dose of anti-PSMA CAR-T cells to target PSMA positive tumors and tumor microenvironment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 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>Number of patients with adverse events.</measure>
    <time_frame>3 year</time_frame>
    <description>Determine the toxicity profile the 4SCAR-PSMA cells with Common Toxicity Criteria for Adverse Effects version 4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor effects</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>
  <secondary_outcome>
    <measure>The expansion and persistence of 4SCAR-PSMA T cells</measure>
    <time_frame>1 year</time_frame>
    <description>Scale of CAR copies and tumor burden (for efficacy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time of the patients</measure>
    <time_frame>3 year</time_frame>
    <description>The survival time of the patients treated with the 4SCAR-PSMA T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>PSMA Positive Tumors or Tumor Tissues</condition>
  <arm_group>
    <arm_group_label>4SCAR-PSMA Cell Therapy for PSMA positive tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of 4SCAR-PSMA T cells at 10^6 cells/kg body weight via IV</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4SCAR-PSMA T cells</intervention_name>
    <description>Infusion of 4SCAR-PSMA T cells at 10^6 cells/kg body weight via IV</description>
    <arm_group_label>4SCAR-PSMA Cell Therapy for PSMA positive tumor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with tumors have received standard first-line therapy and have been judged to&#xD;
             be non-respectable, metastatic, progressive or recurrent.&#xD;
&#xD;
          2. The expression status of PSMA antigens in the tumor tissue will be determined for&#xD;
             eligibility. Positive expression is defined by PMSA antibody staining results based on&#xD;
             immunohistochemistry or flow cytometry analyses.&#xD;
&#xD;
          3. Body weight greater than or equal to 10 kg.&#xD;
&#xD;
          4. Age: ≥1 year and ≤ 75 years of age at the time of enrollment.&#xD;
&#xD;
          5. Life expectancy: at least 8 weeks.&#xD;
&#xD;
          6. Prior Therapy:&#xD;
&#xD;
             There is no limit to the number of prior treatment regimens. Any grade 3 or 4&#xD;
             non-hematologic toxicity of any previous therapy must have resolved to grade 2 or&#xD;
             less.&#xD;
&#xD;
          7. Participant must not have received hematopoietic growth factors for at least 1 week&#xD;
             prior to mononuclear cells collection.&#xD;
&#xD;
          8. At least 7 days must have elapsed since the completion of therapy with a biologic&#xD;
             agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive&#xD;
             regimen.&#xD;
&#xD;
          9. At least 4 weeks must have elapsed since prior therapy that included a monoclonal&#xD;
             antibody.&#xD;
&#xD;
         10. At least 1 week since any radiation therapy at the time of study entry.&#xD;
&#xD;
         11. Karnofsky/jansky score of 60% or greater.&#xD;
&#xD;
         12. Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55&#xD;
             percent.&#xD;
&#xD;
         13. Pulse Ox greater than or equal to 90% on room air.&#xD;
&#xD;
         14. Liver function: defined as alanine transaminase (ALT) &lt;3x upper limit of normal (ULN),&#xD;
             aspartate aminotransferase (AST) &lt;3x ULN; serum bilirubin and alkaline phosphatase &lt;2x&#xD;
             ULN.&#xD;
&#xD;
         15. Renal function: Patients must have serum creatinine less than 3 times upper limit of&#xD;
             normal.&#xD;
&#xD;
         16. Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul,&#xD;
             Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by&#xD;
             transfusion).&#xD;
&#xD;
         17. Patients with known bone marrow metastatic disease will be eligible for study as long&#xD;
             as they meet hematologic function criteria, and the marrow disease does not have&#xD;
             hematologic toxicity.&#xD;
&#xD;
         18. For all patients enrolled in this study, themselves or their parents or legal&#xD;
             guardians must sign an informed consent and assent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.)&#xD;
             or major organ dysfunction, or greater than grade 2 hematologic toxicity.&#xD;
&#xD;
          2. Untreatable central nervous system (CNS) metastasis: Patients with previous CNS tumor&#xD;
             involvement that has been treated and is stable for at least 6 weeks following&#xD;
             completion of therapy are eligible.&#xD;
&#xD;
          3. Previous treatment with other genetically engineered PSMA-specific CAR T cells or&#xD;
             antibody therapy.&#xD;
&#xD;
          4. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled&#xD;
             infection.&#xD;
&#xD;
          5. Patients who require systemic corticosteroid or other immunosuppressive therapy.&#xD;
&#xD;
          6. Evidence of tumor potentially causing airway obstruction.&#xD;
&#xD;
          7. Inability to comply with protocol requirements.&#xD;
&#xD;
          8. Insufficient CAR T cells availability.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</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 of 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>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>chimeric antigen receptor</keyword>
  <keyword>adoptive T cell transfer</keyword>
  <keyword>PSMA</keyword>
  <keyword>Prostate cancer</keyword>
  <keyword>Tumor microenvironment</keyword>
  <keyword>CAR</keyword>
  <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/NCT04429451
org study id: GIMI-IRB-20003
nct id: NCT04429451
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
      PSMA-specific CAR-T cell therapy in patients with PSMA positive tumor. Another goal of the
      study is to learn more about the function of the PSMA CAR-T cells and their persistency in
      the patients.
Prostate-specific membrane antigen (PSMA) is expressed in normal prostate and is upregulated
      in prostate tumor. Therefore, PSMA is a promising target for antigen-specific immunotherapy
      in patients with prostate cancer. However, it has been reported that PSMA expression is not
      restricted to prostate cancer and PSMA is often enriched in the tumor stromal environment. By
      immunostaining, we found that PSMA is expressed in a variety of solid tumors, including brain
      tumor, neuroblastoma and some lymphoma tumor tissues.

      This study aims to use T cells obtained directly from the patient, which can be genetically
      modified to express PSMA-specific chimeric antigen receptor (CAR). The CAR molecules enable
      the T cells to recognize and kill tumor cells or tumor stromal tissues through the
      recognition of a surface antigen, PSMA. This study will evaluate the side effects and the
      best dose of anti-PSMA CAR-T cells to target PSMA positive tumors and tumor microenvironment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with adverse events.
time frame: 3 year
description: Determine the toxicity profile the 4SCAR-PSMA cells with Common Toxicity Criteria for Adverse Effects version 4.0
measure: Anti-tumor effects
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.
measure: The expansion and persistence of 4SCAR-PSMA T cells
time frame: 1 year
description: Scale of CAR copies and tumor burden (for efficacy)
measure: Survival time of the patients
time frame: 3 year
description: The survival time of the patients treated with the 4SCAR-PSMA T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.
arm group label: 4SCAR-PSMA Cell Therapy for PSMA positive tumor
arm group type: Experimental
description: Infusion of 4SCAR-PSMA T cells at 10^6 cells/kg body weight via IV
intervention type: Biological
intervention name: 4SCAR-PSMA T cells
description: Infusion of 4SCAR-PSMA T cells at 10^6 cells/kg body weight via IV
arm group label: 4SCAR-PSMA Cell Therapy for PSMA positive tumor
criteria: 
gender: All
minimum age: 1 Year
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
sharing ipd: No