The Safety and Efficacy Assessment of Allogeneic γδ T Cells Combined With Targeted Therapy and Immunotherapy in Hepatocellular Carcinoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 主要终点
- Safety evaluation: Incidence of Adverse events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of allogeneic γδ T cells combined with targeted therapy and PD-1 monoclonal antibody in first-line treatment of patients with hepatocellular carcinoma.
详细描述
This is a double-arm, single-center, randomized, open label phase I clinical trial to evaluate the efficacy and safety of the combination of ex-vivo expanded allogeneic γδ T cells plus targeted therapy and PD-1 monoclonal antibody in patients with BCLC stage B or C hepatocellular carcinoma (HCC). A typical 3+3 dose-escalation design will be used to determine the optimal dose level of γδ T cells based on the incidence of dose-limiting toxicity (DLT). The initial infusion dose level will start from 1×10^8/kg to 4×10^8/kg in every 3 weeks.
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
- 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
- •Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study.
- •Age 18 years up to the age of 75 (≤75), gender unlimited.
- •Hepatocellular Carcinoma diagnosed according to the 2018 edition of the EASL guidelines.
- •BCLC stage B or C.
- •Liver function: Child-Pugh class A/B (5-9).
- •Eastern Cooperative Oncology Group (ECOG) Performance score≤
- •No previous antitumor therapy.
- •Life expectancy ≥ 6 months.
- •Patients combined with HBV infection require antiviral treatment with nucleoside analogues; patients combined with HCV infection require direct-acting antiviral agent (DAA) treatment.
- •Adequate organ and marrow function (within 4 weeks prior to study treatment initiation).
- •Male and female patients of reproductive potential must agree to use birth control during the study and for at least 30 days post study.
- •Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
- •Be willing to signed a written informed consent document before enrollment.
排除标准
- •Patients combined with HAV, HEV, HIV or other infectious diseases.
- •Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening.
- •Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
- •Major organs dysfunction.
- •Combined with other severe organic diseases or mental illnesses, including any uncontrolled clinically significant systematic 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 6 months prior to screening or during the study; 6 months prior to screening accepted other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.
- •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
γδ T cells+ PD-1 monoclonal antibody+ targeted drugs
Patients will receive 4 cycles of ex-vivo expanded allogeneic γδ T cells treatments, at three-weeks' intervals. Ex-vivo expanded γδ T cells are transfused to patients in a typical 3+3 dose-escalation design (Dose escalation, 1×10^8/kg, 2×10^8/kg,4×10^8/kg).
干预措施: γδ T cells (Biological)
γδ T cells+ PD-1 monoclonal antibody+ targeted drugs
Patients will receive 4 cycles of ex-vivo expanded allogeneic γδ T cells treatments, at three-weeks' intervals. Ex-vivo expanded γδ T cells are transfused to patients in a typical 3+3 dose-escalation design (Dose escalation, 1×10^8/kg, 2×10^8/kg,4×10^8/kg).
干预措施: Targeted drugs (Drug)
γδ T cells+ PD-1 monoclonal antibody+ targeted drugs
Patients will receive 4 cycles of ex-vivo expanded allogeneic γδ T cells treatments, at three-weeks' intervals. Ex-vivo expanded γδ T cells are transfused to patients in a typical 3+3 dose-escalation design (Dose escalation, 1×10^8/kg, 2×10^8/kg,4×10^8/kg).
干预措施: PD-1 monoclonal antibody (Drug)
PD-1 monoclonal antibody+ targeted drugs
PD-1 monoclonal antibody+ targeted drugs
干预措施: Targeted drugs (Drug)
PD-1 monoclonal antibody+ targeted drugs
PD-1 monoclonal antibody+ targeted drugs
干预措施: PD-1 monoclonal antibody (Drug)
结局指标
主要结局
Safety evaluation: Incidence of Adverse events (AEs)
时间窗: up to 60 weeks
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Safety evaluation: Dose limited toxicity (DLTs)
时间窗: up to 60 weeks
The incidence, characteristic and severity of DLTs will be recorded and assessed.
Efficacy evaluation: Duration of Response(DOR)
时间窗: up to 15months
The duration of objective response in patients will be recorded until 15months after the start of 1st cycle of treatment
Efficacy evaluation: Progress Free Survival(PFS)
时间窗: up to 15months
Observation for progression-free survival (PFS) will be recorded until 15 months after the start of 1st cycle of treatment
Safety evaluation: Maximum-tolerated dose (MTD)
时间窗: up to 60 weeks
MTD or clinical recommended dose will be recorded and evaluated.
Efficacy evaluation: Objective Response Rate(ORR)
时间窗: up to 15months
Objective clinical response will be assessed by investigators
Efficacy evaluation: Overall Survival (OS)
时间窗: up to 15months
Observation for overall survival l (OS) will be recorded until 15 months after the start of 1st cycle of treatment.
次要结局
未报告次要终点