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

Prior treatment

• The patient is receiving therapy of other new drugs;
• Patients who need immunosuppressive drugs because of GVAD;
• Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled steroids;
• Previous treatment with any gene therapy;
• Patients previously experienced toxicity from cyclophosphamide;

Other illness

• The disease is progresseing rapidly;
• Epilepsy history or other CNS diseases;
• Uncontrolled active infection;
• Active hepatitis B virus,hepatitis C virus and HIV infection;
• Patients who have other uncontrolled diseases would preclude participation as outlined;
• In condition that may bring risks to subjects or interference to clinical trials.

Lab values

• History of long QT syndrome or severe heart diseases;
• Creatinine\>2.5mg/dl or ALT/AST\>3 times normal or bilirubin\>2.0 mg/dl;

Other

• Evidence of tumor potentially causing airway obstruction;
• Pregnant or lactating women;
• Patients who have CNS sarcoma;

• 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.