<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/NCT04433221</url>
  </required_header>
  <id_info>
    <org_study_id>GIMI-IRB-20007</org_study_id>
    <nct_id>NCT04433221</nct_id>
  </id_info>
  <brief_title>Combination Immunotherapy Targeting Sarcomas</brief_title>
  <official_title>Safety and Efficacy Evaluation of a Combination Immunotherapy Targeting Sarcomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shenzhen Geno-Immune Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <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>
    <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 aim of this clinical trial is to assess the feasibility, safety and efficacy of a&#xD;
      combination low dose chemotherapy and immunotherapy in patients who have sarcoma that is&#xD;
      relapsed or late staged. Another goal of the study is to assess the safety and efficacy of&#xD;
      the therapy that combines multiple CAR T cells followed by sarcoma vaccines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with late staged and/or recurrent sarcoma have poor prognosis despite complex&#xD;
      multimodal therapy. Therefore, innovative interventions are needed. Sarcoma is known to&#xD;
      express increased levels of surface antigens that can be targeted by CAR-T cells. In&#xD;
      addition, studies have shown that low dose chemotherapy such as doxorubicin may modulate&#xD;
      surface PD-L1 level and enhance immunotherapy effects. This study will combine multiple CAR T&#xD;
      cells with low dose chemotherapy to treat sarcoma, and followed by maintenance sarcoma&#xD;
      vaccines. The purpose of this clinical trial will assess the feasibility, safety, efficacy&#xD;
      and side effects of this combination therapy in patients who have sarcoma that is relapsed or&#xD;
      late staged.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">July 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 CART cells infusion</measure>
    <time_frame>3 months</time_frame>
    <description>Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival Rate</measure>
    <time_frame>1 year</time_frame>
    <description>Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment response rate of sarcomas</measure>
    <time_frame>1 year</time_frame>
    <description>Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on CT imaging analysis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Sarcoma</condition>
  <condition>Osteoid Sarcoma</condition>
  <condition>Ewing Sarcoma</condition>
  <arm_group>
    <arm_group_label>Multiple sarcoma-specific CAR-T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who have confirmed surface antigens including GD2, PSMA, Her2, CD276 or other markers</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Multiple sarcoma-specific CAR-T cells and sarcoma vaccines</intervention_name>
    <description>1 infusion, CART 1x10^6~1x10^7 cells/kg via IV and vaccines 1-5x10^6 irradiated cells via subcutaneous injection</description>
    <arm_group_label>Multiple sarcoma-specific CAR-T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Stage Ⅲ，Ⅳ sarcoma patients or recurrent sarcoma patients;&#xD;
&#xD;
          2. Age: ≥ 6 months and ≤80 years of age at the time of enrollment;&#xD;
&#xD;
          3. At least 2 weeks since the last standard chemotherapy or radiotherapy and&#xD;
             immunosuppressive therapy such as steroid hormone before enrollment;&#xD;
&#xD;
          4. Side effects of chemotherapy have been well managed;&#xD;
&#xD;
          5. Confirmed malignant cell expression of CART target antigens by IHC or flow&#xD;
&#xD;
          6. Karnofsky /jansky score of 50% or greater;&#xD;
&#xD;
          7. Expected survival &gt; 8 weeks;&#xD;
&#xD;
          8. ANC≥ 1×10^6/L，PLT ≥ 1×10^8/L;&#xD;
&#xD;
          9. Pulse oximetry of≥90% on room air；&#xD;
&#xD;
         10. Adequate hepatic function, defined as aspartate aminotransferase(AST)&lt; 5 times upper&#xD;
             limit of normal(ULN),serum bilirubin &lt; 3 times ULN;&#xD;
&#xD;
         11. Adequate renal function, defined as serum creatinine less than 2 times ULN, if serum&#xD;
             creatinine more than 1.5 times ULN, creatinine clearance rate test is needed;&#xD;
&#xD;
         12. Patients must have sufficient autologous CART cells at does greater than 0.5x10^6&#xD;
             cells/kg body weight;&#xD;
&#xD;
         13. Sign an informed consent and assent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The disease is progressing rapidly;&#xD;
&#xD;
          2. The patient is receiving therapy of other new drugs and under evaluation;&#xD;
&#xD;
          3. Evidence of tumor potentially causing airway obstruction;&#xD;
&#xD;
          4. Epilepsy history or other CNS diseases;&#xD;
&#xD;
          5. Patients who need immunosuppressive drugs;&#xD;
&#xD;
          6. History of long QT syndrome or severe heart diseases;&#xD;
&#xD;
          7. Uncontrolled active infection;&#xD;
&#xD;
          8. Active hepatitis B virus, hepatitis C virus or HIV infection;&#xD;
&#xD;
          9. Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled&#xD;
             steroids;&#xD;
&#xD;
         10. Previous treatment with any gene therapy;&#xD;
&#xD;
         11. Creatinine&gt;2.5mg/dl or ALT/AST&gt;3 times normal or bilirubin&gt;2.0 mg/dl;&#xD;
&#xD;
         12. Patients who have other uncontrolled diseases such as obstruction of lung function&#xD;
             would preclude participation as outlined;&#xD;
&#xD;
         13. Pregnant or lactating women;&#xD;
&#xD;
         14. Patients previously experienced toxicity from cyclophosphamide and doxorubicin;&#xD;
&#xD;
         15. Patients who have CNS sarcoma;&#xD;
&#xD;
         16. In condition that may bring risks to subjects or interference to clinical trials.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Lung-Ji Chang, MD</last_name>
    <phone>86-(0755)86725195</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>Xiuli Yuan, MD</last_name>
      <phone>86-18938690212</phone>
      <email>18938690212@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 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 12, 2020</last_update_submitted>
  <last_update_submitted_qc>June 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sarcoma</keyword>
  <keyword>Chemotherapy</keyword>
  <keyword>Doxorubicin</keyword>
  <keyword>CART</keyword>
  <keyword>Vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</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/NCT04433221
org study id: GIMI-IRB-20007
nct id: NCT04433221
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this clinical trial is to assess the feasibility, safety and efficacy of a
      combination low dose chemotherapy and immunotherapy in patients who have sarcoma that is
      relapsed or late staged. Another goal of the study is to assess the safety and efficacy of
      the therapy that combines multiple CAR T cells followed by sarcoma vaccines.
Patients with late staged and/or recurrent sarcoma have poor prognosis despite complex
      multimodal therapy. Therefore, innovative interventions are needed. Sarcoma is known to
      express increased levels of surface antigens that can be targeted by CAR-T cells. In
      addition, studies have shown that low dose chemotherapy such as doxorubicin may modulate
      surface PD-L1 level and enhance immunotherapy effects. This study will combine multiple CAR T
      cells with low dose chemotherapy to treat sarcoma, and followed by maintenance sarcoma
      vaccines. The purpose of this clinical trial will assess the feasibility, safety, efficacy
      and side effects of this combination therapy in patients who have sarcoma that is relapsed or
      late staged.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of CART cells infusion
time frame: 3 months
description: Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
measure: Overall survival Rate
time frame: 1 year
description: Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
measure: Treatment response rate of sarcomas
time frame: 1 year
description: Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on CT imaging analysis.
arm group label: Multiple sarcoma-specific CAR-T cells
arm group type: Experimental
description: Patients who have confirmed surface antigens including GD2, PSMA, Her2, CD276 or other markers
intervention type: Biological
intervention name: Multiple sarcoma-specific CAR-T cells and sarcoma vaccines
description: 1 infusion, CART 1x10^6~1x10^7 cells/kg via IV and vaccines 1-5x10^6 irradiated cells via subcutaneous injection
arm group label: Multiple sarcoma-specific CAR-T cells
criteria: 
gender: All
minimum age: 1 Year
maximum age: 75 Years
healthy volunteers: No
last name: Lung-Ji Chang, MD
phone: 86-(0755)86725195
email: c@szgimi.org
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Sarcoma, Ewing
sharing ipd: No