A Single-arm Pilot Clinical Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy
试验速览
- 阶段
- 1 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of patients with adverse event
研究概览
简要总结
The purpose of this study is to collect the date on the safety and potential effectiveness of CART cells combined with interventional therapy in patients with advanced liver malignancy.
详细描述
Designer T cells are prepared by PBMC which from patients or suitable donator by leukapheresis, and then activated and re-engineered to express chimeric antigen receptors (CARs). There are three options for CAR-targets: GPC3 for hepatocellular carcinoma; mesothelin for pancreatic cancer metastatic; CEA for colorectal cancer metastatic. Cells are expanded in culture and returned to the participant by vascular interventional therapy or by intra-tumor injection at the dose of （1.25~4）×107 CAR positive T cells/cm3 tumor bulk. The volume of cell products and the time of cell perfusion process lasted would depend on the ways of cell perfused.
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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •tumor histological examination confirmed as GPC3/ mesothelin/CEA positive expression;
- •persistent cancer after at least one prior standard of care chemotherapy, has no willing for surgery or cannot be suitable for surgery patients
- •life expectancy greater than 6 months
- •satisfactory organ and bone marrow function as defined by the following: (1) creatinine <1.5mg/dl; (2) cardiac ejection fraction of >55%; (3) hemoglobin>9g/dl, bilirubin 2.0×the institution normal upper limit
- •without bleeding disorder or coagulation disorders
- •Don't allergy to Radiocontrast agent
- •birth control
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis
- •Voluntary informed consent is given
排除标准
- •Pregnant or lactating women
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- •patients in the situation of: (1) 30 days before apheresis is still in the period of other antitumor drug observation; (2) patient dont recuperate from earlier acute adverse influence brought by any treatments accepted before
- •Four weeks before recruit accepted radiation therapy
- •Previously treatment with any gene therapy products
- •Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
- •Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade III or IV cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases, CNS diseases)
- •Patient with severe acute hypersensitive reaction
- •Taking part in other clinical trials
- •Study leader considers not suitable for this tiral
研究组 & 干预措施
CAR-T for liver cancer
A single dose of CART cells will be administered by vascular interventional therapy or by intra-tumor injection with a dose of （1.25~4）×107 CAR positive T cells/cm3 tumor bulk. The volume of cell products and the time of cell perfusion process lasted would depend on the ways of cell perfused. And an interventional radiologist would operate the cell infusion.
干预措施: CAR-T cell (Drug)
结局指标
主要结局
Number of patients with adverse event
时间窗: 6 weeks
adverse event is evaluated with CTCAE, version 4.0
次要结局
- Number of patients with tumor response(8 weeks)
- Detection of transferred T cells in the circulation using quantitative -PCR(8 weeks)