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Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas

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ClinicalTrials.gov Identifier: NCT03356782
Recruitment Status : Recruiting
First Posted : November 29, 2017
Last Update Posted : June 11, 2020
Information provided by (Responsible Party):
Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information
First Submitted Date  ICMJE November 24, 2017
First Posted Date  ICMJE November 29, 2017
Last Update Posted Date June 11, 2020
Actual Study Start Date  ICMJE December 1, 2017
Estimated Primary Completion Date November 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 24, 2017)
Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [ Time Frame: 3 months ]
Physiological parameter (measuring cytokine response)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2017)
Persistence and proliferation of CART cells in patients [ Time Frame: 3 months ]
The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 24, 2017)
Anti-tumor effects [ Time Frame: 1 year ]
Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Official Title  ICMJE Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Brief Summary The aim of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cells 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 CAR T cells and IgT cells to treat sarcoma.
Detailed Description Patients with late staged and/or recurrent sarcoma have poor prognosis despite complex multimodal therapy. Therefore, novel curative approaches are needed.This study will combine two different ways to fight sarcoma: antibodies and CAR-T cells. Several immune checkpoint antibodies have been examined on various tumors with good outcomes. Sarcoma is known to express increased levels of surface antigens that can be targeted by CAR-T cells. Thus, in this study, the 4SCAR-IgT cells targeting sarcoma surface antigens will be infused in dose escalation cohorts.This study will assess the feasibility, safety, efficacy and side effects of CAR T cells immunotherapy in patients who have sarcoma that is relapsed or late staged.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sarcoma
  • Osteoid Sarcoma
  • Ewing Sarcoma
Intervention  ICMJE Biological: Sarcoma-specific CAR-T cells
1 infusion, for 1x10^6~1x10^7 cells/kg via IV
Study Arms  ICMJE Experimental: Sarcoma-specific CAR-T cells
Peripheral blood mononuclear cells (PBMCs) of patients who have CD133, GD2, Muc1, CD117 or other marker positive sarcoma will be obtained through apheresis, and T cells will be activated and modified to sarcoma-specific CAR-T cells.
Intervention: Biological: Sarcoma-specific CAR-T cells
Publications * Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 24, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date November 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Stage Ⅲ,Ⅳ sarcoma patients or recurrent sarcoma patients;
  2. Age: ≥ 18 and ≤65 years of age at the time of enrollment;
  3. At least 4 weeks since any chemotherapy or radiotherapy and at least 1 week since immunosuppressive therapy such as using steroid hormone before enrollment;
  4. Side effects of chemotherapy have been well managed;
  5. Malignant cells are target antigen positive(higher than ++) confirmed by IHC, quantitative PCR or sequencing;
  6. Karnofsky /jansky score of 50% or greater;
  7. Expected survival > 6 weeks;
  8. ANC≥ 1×10^6/L,PLT ≥ 1×10^8/L;
  9. Pulse oximetry of≥90% on room air;
  10. Adequate hepatic function,defined as aspartate aminotransferase(AST)< 5 times upper limit of normal(ULN),serum bilirubin < 3 times ULN;
  11. Adequate renal function,defined as serum creatinine less than 2 times ULN,if serum creatinine more than 1.5 times ULN,creatinine clearance rate test is needed;
  12. Patients must have autologous transduced T cells at levels greater than 15%;
  13. Sign an informed consent and assent.

Exclusion Criteria:

  1. The disease is progresseing rapidly;
  2. The patient is receiving therapy of other new drugs;
  3. Evidence of tumor potentially causing airway obstruction;
  4. Epilepsy history or other CNS diseases;
  5. Patients who need immunosuppressive drugs because of GVAD;
  6. History of long QT syndrome or severe heart diseases;
  7. Uncontrolled active infection;
  8. Active hepatitis B virus,hepatitis C virus and HIV infection;
  9. Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled steroids;
  10. Previous treatment with any gene therapy;
  11. Creatinine>2.5mg/dl or ALT/AST>3 times normal or bilirubin>2.0 mg/dl;
  12. Patients who have other uncontrolled diseases would preclude participation as outlined;
  13. Pregnant or lactating women;
  14. Patients previously experienced toxicity from cyclophosphamide;
  15. Patients who have CNS sarcoma;
  16. In condition that may bring risks to subjects or interference to clinical trials.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lung-Ji Chang, PhD 86-075586725195 c@szgimi.org
Listed Location Countries  ICMJE China
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03356782
Other Study ID Numbers  ICMJE GIMI-IRB-17016
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Shenzhen Geno-Immune Medical Institute
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute
PRS Account Shenzhen Geno-Immune Medical Institute
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP