A Clinical Study of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
研究概览
简要总结
The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.
详细描述
This is a combined phase 1 and 2 clinical study. The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer. The treatment outcomes will be compared.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC).
- •Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than
- •Patients have a life expectancy > 12 weeks.
- •Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
- •Negative pregnancy test for females of child-bearing potentials.
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
- •Signed informed consent form.
排除标准
- •Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
- •Patients with symptomatic central nervous system (CNS) involvement.
- •Pregnant or nursing women.
- •Known HIV infection.
- •Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
- •History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- •Previously treatment with any gene therapy products.
- •The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
- •Patients with a history of organ transplantation or are waiting for organ transplantation.
研究组 & 干预措施
CAR-T
Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.
干预措施: CAR-T Cells (Biological)
CAR-T combining PD-1 knockout
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
干预措施: CAR-T Cells (Biological)
CAR-T combining PD-1 knockout
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
干预措施: CAR-T combining PD-1 Knockout (Combination Product)
CAR-T combining PD-1 knockout
Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
干预措施: PD-1 knockout (Biological)
PD-1 knockout
PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
干预措施: PD-1 knockout (Biological)
PD-1 mAb
Patients will be treated with a FDA approved monoclonal antibody for an identical course of treatment. This group will serve as PD-1 antibody treated group.
干预措施: PD-1 mAb (Drug)
Sham Control
Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.
干预措施: Sham control (Other)
结局指标
主要结局
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
时间窗: approximately 6 months
Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.
次要结局
- Overall Survival - OS(Up to 24 months)
- Median CAR-T cell persistence(4 years)
- Response Rate(6 months)
- Progression free survival - PFS(Up to 12 months)
研究者
Size Chen
Professor
The First Affiliated Hospital of Guangdong Pharmaceutical University