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

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

Tracking Information

• First Submitted Date: November 24, 2017
• First Posted Date: November 29, 2017
• Last Update Posted Date: June 11, 2020
• Actual Study Start Date: December 1, 2017
• Estimated Primary Completion Date: November 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: 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: Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sarcoma
• Osteoid Sarcoma
• Ewing Sarcoma

Intervention

Biological: Sarcoma-specific CAR-T cells

1 infusion, for 1x10^6~1x10^7 cells/kg via IV

Study Arms

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 24, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: November 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 1 Year to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03356782
• Other Study ID Numbers: 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

• 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: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang, PhD; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: June 2020