Single-center, Open Clinical Study on the Efficacy and Safety of c-Met/PD-L1 Chimeric Antigen Receptor T Cell Injection in the Treatment of Primary Hepatocellular Carcinoma
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 50
- 主要终点
- The efficacy of c-Met/PD-L1 CAR-T cells in the treatment of HCC
研究概览
简要总结
Title: Single-center, open clinical study on the efficacy and safety of c-Met/PD-L1 T cell injection in the treatment of primary hepatocellular carcinoma
Stage: Phase I clinical trial
Purpose: To evaluate the efficacy and safety of c-Met/PD-L1 CAR-T cells in patients with primary hepatocellular carcinoma
Object: patients with primary hepatocellular carcinoma
Sample size: 50 cases
Number of centres：1
Study design: CT, MRI, PET and blood biochemical tests were performed before treatment to evaluate the state of HCC. Peripheral blood of the patient was extracted and PBMC was isolated. CAR-T cells were obtained by tranducing PBMC with c-Met/PD-L1 CAR lentivirus, and the proliferation capacity and immune phenotype of the cells were tested. After passing the inspection, the cells were re-injected into the patient three times. The efficacy and safety of c-Met/PD-L1 CAR-T cells was assessed respectively at 4 week, 12 week, 24 week and 48 week after treatment.
Trial product: c-Met/PD-L1 CAR-T cells
Course of treatment: 3 days for a course of treatment, only one course of treatment. A second course is given as appropriate if the treatment is beneficial to the patient.
详细描述
Title: Single-center, open clinical study on the efficacy and safety of c-Met/PD-L1 CAR-T cell injection in the treatment of primary hepatocellular carcinoma
Research purpose:
Primary outcome:
To evaluate the efficacy of c-Met/PD-L1 CAR-T cell injection in the treatment of primary hepatocellular carcinoma.
Secondary purpose:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 18 to 70 years (including 18 and 70 years);
- •Immune histochemistry detection was confirmed as c-met positive ; hepatocellular carcinoma, and the patient has no effective treatment at present
- •Liver tissue type: non-diffuse hepatocellular carcinoma, no extra hepatic metastasis or portal vein infiltration;
- •Cirrhosis of the liver: child-pugh A grade or child-pugh B grade, child-pugh-turcotte score <7;
- •Routine blood test: white blood cell count (WBC) or 3 * 10^9/L, lymphocyte percentage (LY) 15% or higher, hemoglobin (Hb), 90g/L or higher, prothrombin time (PT), international standardization ratio (INR) 1.7 or less, or prothrombin time (PT) extend the 4 s or less, lymphocyte acuity 0.8 * 10^9/L;
- •The main tissues and organs of the patients are functioning well (if the organs do not meet the following standards, but the researchers believe that the diseases themselves can be included):
- •Hepatic and pancreatic functions: alanine aminotransferase/aspartate aminotransferase (ALT/AST) is 5 times of normal value, total bilirubin (TBiL) is 3.0mg/dL, albumin (ALB) is 35g/L, serum lipase is 1.5 times of normal value, and serum amylase is 1.5 times of normal value. Renal function: creatinine <2 ULN
- •Lung function: indoor oxygen saturation greater than or equal to 95% (without oxygen inhalation)
- •Cardiac function: LVEF is greater than or equal to 40%
- •The absolute number of neutrophils is greater than or equal to 0.75 * 10^9/L, and platelets are greater than or equal to 50 * 10^9/L
- •ECOG score 0-1 or Karnofsky performance status (card score) (KPS) is greater than 60, and the expected survival time is greater than or equal to 12 weeks;
- •There are adequate venipuncture or venous sampling channels and no contraindications for lymphocyte separation;
- •No anti-tumor therapy, including chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs), was received within 4 weeks before enrollment, and the toxicity response of previous treatment was restored to level 1 or less (except for low-level toxicity such as hair loss);
- •Female subjects of reproductive age must have negative serum or urine pregnancy test during screening, and male and female patients agree to take effective contraceptive measures during the trial;
- •There were no other serious complications;
- •Voluntarily sign informed consent.
排除标准
- •Women during pregnancy (positive urine/blood pregnancy test) or lactation; A male or female who has a plan to conceive within the last 1 year; Effective contraceptive (condom or birth control pill, etc.) cannot be guaranteed for 1 year after enrollment;
- •The patients had uncontrollable infection within 4 weeks before enrollment. However, prophylactic antibiotics, antiviral and antifungal infection treatment are allowed; Active hepatitis b hepatitis c; People infected with human immunodeficiency virus (HIV);
- •Suffering from severe autoimmune disease or immunodeficiency disease;
- •The patient is allergic to large molecular biological drugs such as antibodies or cytokines;
- •The patient who has mentally ill;
- •The patient has substance abuse/addiction;
- •The patient who has a history of hepatocellular carcinoma;
- •Having severe peptic ulcer or bleeding;
- •A patient who receives an organ transplant or waits for one;
- •Patients requiring anticoagulation (e.g., warfarin or heparin);
- •Patients requiring long-term antiplatelet therapy (aspirin > 300 mg/d; Clopidogrel dose > 75 mg/d);
- •Organ failure patient:
- •Cardiac function: grade 3 or above according to the New York heart association (NYHA) standard
- •Liver function: C level above, according to child-pugh standard
- •Chronic kidney disease (CKD) stage 4 or above; Renal insufficiency or above
- •Lung function: severe respiratory failure, involving other organs
- •Brain function: abnormal central nervous system or disturbance of consciousness;
- •Systemic use of hormones within 4 weeks before enrollment (use of prednisone 20mg/ d or less is allowed, except for inhaled hormones);
- •The patient participated in other clinical trials within 4 weeks before enrollment;
- •The patient has been treated with radiation for the past four weeks;
- •Investigators determined that the patient was unable or unwilling to comply with protocol requirements.
研究组 & 干预措施
c-Met/PD-L1 CAR-T cells treating group
Intervention Name:c-Met/PD-L1 CAR-T cell injection dosage form: injection dosage:The backtransfusion dose (recommended dose: 2 * 10^6/kg) was determined by the investigator based on the subject's own/disease condition and in vitro preparation.
干预措施: c-Met/PD-L1 CAR-T cell injection (Biological)
结局指标
主要结局
The efficacy of c-Met/PD-L1 CAR-T cells in the treatment of HCC
时间窗: 6 months after treatment
assessing the efficacy of c-Met/PD-L1 CAR-T cells through overall survival
次要结局
- the incidence of treatment-emergent adverse events of c-Met/PD-L1 T cell injection in the treatment of HCC(6 months after treatment)
- The amplification and persistence of c-Met/PD-L1 CAR-T cell in the subjects varied with time(6 months after treatment)
研究者
LiTao
Principal Investigator
The Second Hospital of Nanjing Medical University