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

NCT ID: NCT03356782

Last Updated: 2020-06-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2023-12-31

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.

Conditions

Sarcoma; Osteoid Sarcoma; Ewing Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sarcoma-specific CAR-T cells

Intervention Type: BIOLOGICAL

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

Interventions

Sarcoma-specific CAR-T cells

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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Lung-Ji Chang

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lung-Ji Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Locations

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

c@szgimi.org

86-075586725195

Facility Contacts

Lung-Ji Chang, PhD

Role: primary

c@szgimi.org

86-075586725195

References

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.

Reference Type: DERIVED

PMID: 31401903 (View on PubMed)

Other Identifiers

GIMI-IRB-17016

Identifier Type: -

Identifier Source: org_study_id