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

NCT03356782 | Unknown Phase 1

• 1 other identifier: GIMI-IRB-17016
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcoma; Osteoid Sarcoma; Ewing Sarcoma

Keywords

CART; PD-1; PDL-1; CTLA-4; sarcoma; solid tumor

Outcome Measures

Primary Outcomes (1)

• Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

  Physiological parameter (measuring cytokine response)

  3 months

Secondary Outcomes (1)

• Persistence and proliferation of CART cells in patients

  3 months

Other Outcomes (1)

• Anti-tumor effects

  1 year

Study Arms (1)

Sarcoma-specific CAR-T cells

EXPERIMENTAL

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.

Biological: Sarcoma-specific CAR-T cells

Interventions

Sarcoma-specific CAR-T cells BIOLOGICAL

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

Sarcoma-specific CAR-T cells

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• The disease is progresseing rapidly;
• The patient is receiving therapy of other new drugs;
• Evidence of tumor potentially causing airway obstruction;
• Epilepsy history or other CNS diseases;
• Patients who need immunosuppressive drugs because of GVAD;
• History of long QT syndrome or severe heart diseases;
• Uncontrolled active infection;
• Active hepatitis B virus,hepatitis C virus and HIV infection;
• Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled steroids;
• Previous treatment with any gene therapy;
• Creatinine\>2.5mg/dl or ALT/AST\>3 times normal or bilirubin\>2.0 mg/dl;
• Patients who have other uncontrolled diseases would preclude participation as outlined;
• Pregnant or lactating women;
• Patients previously experienced toxicity from cyclophosphamide;
• Patients who have CNS sarcoma;

Sponsors & Collaborators

• Shenzhen Geno-Immune Medical Institute: lead

Study Sites (1)

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, 518000, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms; Sarcoma, Ewing; Diabetes Mellitus, Insulin-Dependent, 12

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Study Officials

• Lung-Ji Chang, PhD

  Shenzhen Geno-Immune Medical Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lung-Ji Chang, PhD

CONTACT

86-075586725195; c@szgimi.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: November 24, 2017
• First Posted: November 29, 2017
• Study Start: December 1, 2017
• Primary Completion: November 30, 2023
• Study Completion: December 31, 2023
• Last Updated: June 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)