Immunotherapy of Advanced Hepatitis B Related Hepatocellular Carcinoma With γδT Cells
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Overall survival (OS)
研究概览
简要总结
To evaluate the safety, tolerability and efficacy of autologous γδT cells in the treatment of advanced hepatitis B-related hepatocellular carcinoma.
详细描述
This is a single-centre, non-randomised, open label, no control, prospective clinical trial. The study will include the following sequential phases: sign informed consent, γδT cells pre-culture, fresh biopsy and screening, apheresis, γδT cells preparation, treatment and follow-up. The study will evaluate the safety, tolerability and efficacy of autologous γδT cells in patients with advanced hepatitis B related hepatocellular carcinoma (HCC) which are refractory to current treatment.
Stage I comprising a safety cohort of patients to identify a safe dose, Stage II comprising an expanded patient group for response signal identification, Stage III to confirm efficacy and safety.
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
- •Patients should sign informed consent form voluntarily and comply with the requirements of this study.
- •Gender unlimited, age 18 to 70 years old.
- •Hepatocellular carcinoma histopathology proven by liver fresh biopsy.
- •According to the 2018 edition of the EASL guidelines for primary liver cancer, patients were diagnosed with advanced HBV-related hepatocellular carcinoma (BCLC stage B and C) by pathology and imaging; all patients required antiviral therapy with nucleoside analogues; other treatments (e.g. interventional therapy) at least 2 weeks prior to γδT cell infusion; patients can take the first- or second-line targeted drugs recommended by the guidelines, such as lenvatinib or sorafenib.
- •Liver function: Child-Pugh class A/B (5-9), Eastern Cooperative Oncology Group (ECOG) Performance status 0-
- •Expected survival ≥ 6 months.
- •Male and female of reproductive potential must agree to use birth control during the study and for at least 30 days post study.
排除标准
- •Combine other viral liver diseases or other liver disease patients.
- •Acute infection, gastrointestinal bleeding, etc. occurred within 30 days before screening.
- •Pregnant or lactating women; patients after organ transplantation; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
- •Dysfunction of major organs; patient white blood cell count <1.0×10e9/L, platelet count <60×10e9/L, hemoglobin <86g/L, prothrombin time (INR) >2.3, or prolonged clotting time >6 seconds, serum albumin <28g/L, total bilirubin >51mmol/L, ALT/AST >5 times the upper limit of normal, creatinine >1.5 times the upper limit of normal.
- •Combined with other serious organic diseases, mental illnesses, including any uncontrolled clinically significant systemic diseases such as urinary, circulatory, respiratory, neurological, psychiatric, digestive, endocrine and immune diseases.
- •Allergic constitution, history of allergies to blood products, known to be allergic to test substances.
- •Immunosuppressive or systemic cytotoxic drugs may require within six months prior to screening or during treatment; 6 months prior to screening accepted other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.; immunotherapy such as PD-1 and PD-L1 antibodies.
- •Patients currently participating in other clinical trials who may violate this treatment plan and observations.
- •Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.
- •Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed: patients with any serious acute or chronic physical or mental illness, or laboratory abnormalities.
研究组 & 干预措施
Autologous γδT cells
Subjects will receive 3 cycles of γδT cells treatments, at four-week intervals, each cycle has 2 infusions.
Dose escalation subjects will receive 6 infusions with dose of γδT cells escalation from 1×10e9 to 6×10e9.
Constant dose subjects will have single infusion intravenously at a target dose of 1~2×10e9 γδT cells.
干预措施: autologous γδT cells (Biological)
结局指标
主要结局
Overall survival (OS)
时间窗: 14 months
Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
Incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 14 months
Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.
次要结局
- Patients-based Quality of Life Evaluation(14 months)
- Objective Response Rate (ORR)(14 months)