肿瘤细胞治疗研究
英文原题：Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
这是一项 I/II 期注册临床试验，评估 CAR-T 细胞治疗肉瘤的安全性、可行性及初步疗效。当前状态：尚未开始招募。计划入组 20 例。试验地点：中国 · 深圳（共 1 个中心，其中中国 1 个）。登记号：NCT03356782。
不限性别 · ≥ 1 Year 且 ≤ 75 Years
纳入标准： 1. III期、IV期或复发性肉瘤患者。 2. 入组时年龄≥18岁且≤65岁。 3. 入组前末次化疗或放疗后至少间隔4周；末次类固醇激素等免疫抑制治疗后至少间隔1周。 4. 化疗副作用已得到良好控制。 5. 通过免疫组化、定量PCR或测序确认恶性细胞靶抗原阳性（高于++）。 6. Karnofsky/Lansky评分≥50%。 7. 预期生存期>6周。 8. ANC≥1×10^6/L，血小板≥1×10^8/L。 9. 室内空气下脉搏血氧饱和度≥90%。 10. 肝功能足够：AST<正常值上限（ULN）的5倍，总胆红素<ULN的3倍。 11. 肾功能足够：血清肌酐<ULN的2倍；若肌酐>ULN的1.5倍，须进行肌酐清除率检查。 12. 自体转导T细胞水平>15%。 13. 签署知情同意书及同意文件。 排除标准： 1. 疾病快速进展。 2. 正在接受其他新药治疗。 3. 有证据提示肿瘤可能造成气道梗阻。 4. 有癫痫史或其他中枢神经系统疾病。 5. 因GVHD需要使用免疫抑制药物。 6. 有长QT综合征或严重心脏病史。 7. 未控制的活动性感染。 8. 活动性乙型肝炎病毒、丙型肝炎病毒或HIV感染。 9. 入组前2周内接受全身性糖皮质激素治疗（吸入性类固醇除外）。 10. 既往接受过任何基因治疗。 11. 肌酐>2.5 mg/dL、ALT/AST>正常值上限3倍或胆红素>2.0 mg/dL。 12. 存在其他可能妨碍参加研究的未控制疾病。 13. 妊娠或哺乳期女性。 14. 既往环磷酰胺治疗出现毒性。 15. 肉瘤累及中枢神经系统。 16. 可能给受试者带来风险或干扰临床试验的其他情况。
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.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：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
次要终点：Persistence and proliferation of CART cells in patients
通过单采获取表达CD133、GD2、MUC1、CD117或其他标志物的肉瘤患者外周血单个核细胞，随后活化T细胞并进行工程化改造，制备肉瘤特异性CAR-T细胞。
本临床试验旨在评估CAR-T细胞免疫疗法用于复发或晚期肉瘤患者的可行性、安全性和疗效。研究还将评估CAR-T细胞联合IgT细胞治疗肉瘤的安全性和疗效。
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.
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