A Clinical Safety and Efficacy Study of Autologous Tumor Infiltrating Lymphocytes Injection (GC101 TIL) in Patients With r/r Gastrointestinal Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TIL) therapy in patients with malignant refractory/relapsed gastrointestinal tumors. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 years to 75 years;
- •Histologically diagnosed as primary/relapsed/metastasized gastrointestinal tumors ;
- •Expected life-span more than 3 months;
- •Karnofsky≥60% or ECOG score 0-2;
- •Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
- •Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated;
- •At least 1 evaluable tumor lesion;
- •Hematology and Chemistry（within 7 days prior to enrollment）:
- •Absolute count of white blood cells≥2.5×10^9/L;
- •Absolute count of neutropils≥1.5×10^9/L;
- •Absolute count of lymphocytes ≥0.7×109/L；
- •Platelet count≥100×10^9；
- •hemoglobin≥90 g/L;
- •Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
- •International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days);
- •Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min;
- •Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN);
- •Totol bilirubin≤1.5×ULN;
- •no absolute or relative contraindications to operation or biopsy;
- •Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion；
- •Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs;
- •Be able to understand and sign the informed consent document;
- •Be able to stick to follow-up visit plan and other requirements in the agreement.
排除标准
- •Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
- •Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%;
- •Significant cardiovascular anomalies according to any of the following definition: New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
- •Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
- •Severe physical or mental diseases;
- •Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
- •Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
- •History of allergy to chemical compound consisting of chemical and biologic substances resembling cell therapy;
- •Having received immunotherapy and developed irAE level greater than Level 3;
- •Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
- •Females in pregnancy or lactation;
- •History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
- •Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.
研究组 & 干预措施
Tumor Infiltrating Lymphocytes
1x10^9-5x10^10 in vitro expanded autologous TILs will be infused i.v. to patients with relapsed/refractory malignant gastrointestinal tumors after NMA lymphodepletion treatment with hydroxychloroquine(600mg,single-dose) and cyclophosphamide.
干预措施: Tumor Infiltrating Lymphocytes (TIL) (Biological)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to 36 months
The time length between TIL infusion and confirmed subsequent disease progression according to RECIST 1.1
Objective Response Rate (ORR)
时间窗: Up to 36 months
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): ORR (proportion of patients) = # with CR + # with PR / # with CR + # with PR + # with SD + # with PD. ( Except baseline evaluation within 28 days before TIL infusion，PET/CT scan will be performed at 6 weeks after TIL infusion, and than every 6 weeks for 1 year, and then every six months after that for up to 3 years)
Objective Response Rate (ORR)
时间窗: Up to 36 months
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): ORR (proportion of patients) = # with CR + # with PR / # with CR + # with PR + # with SD + # with PD. ( Except baseline evaluation within 28 days before TIL infusion，PET/CT scan will be performed at 6 weeks after TIL infusion, and than every 6 weeks for 1 year, and then every six months after that for up to 3 years)
Progression-Free Survival (PFS)
时间窗: Up to 36 months
The time length between TIL infusion and confirmed subsequent disease progression according to RECIST 1.1
次要结局
- Change in Quality of Life(Up to 36 months)
- Change in Quality of Life(Up to 36 months)
- Duration of Response (DOR)(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)