A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of Adverse Events
研究概览
简要总结
This study enrolls patients who have relapsed/advanced hepatocellular carcinoma (HCC, BCLC stage C). The HCC tumor relapsed or metastasized through the body after standard treatment or the patients cannot receive standard treatment under current conditions. This research study uses special immune system cells called iNKT cells, a new experimental treatment.
The purpose of this study is to find the biggest dose of iNKT cells that is safe and tolerance, to see how long they last in the body, to learn the immunoresponse in the body, to learn the side effects are and to see if the iNKT cells will help people with relapsed/advanced hepatocellular carcinoma (HCC).
详细描述
PBMCs of enrolled patients were collected and then further separated by density gradient centrifugation. After washing three times, the cells were resuspended in serum-free medium with recombinant human IL-2 and α-GalCer. Restimulation with α-GalCer-pulsed autologous DCs was done on days 7. After 14 days of cultivation, the iNKT cells were harvested, washed thrice, and then resuspended in saline. The frequency of iNKT cells before and after cultured in vitro were determined by flow cytometry analysis.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years.
- •Patients with hepatocellular carcinoma (BCLC, stage C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time.
- •Life expectancy of ≥ 12 weeks.
- •WBC>3.5×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value.
- •iNKT>10/mL in peripheral blood mononuclear cell (PBMC).
- •Able to understand and sign the informed consent.
排除标准
- •Any uncontrolled systematic disease: hypertension, heart disease, and et al.;
- •Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors;
- •Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment;
- •Unstable immune systematic diseases or infectious diseases;
- •Combined with AIDS or syphilis;
- •Patients with history of stem cell or organ transplantation;
- •Patients with allergic history to related drugs and immunotherapy;
- •Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage;
- •Pregnant or lactating subjects;
- •Unsuitable subjects considered by clinicians.
研究组 & 干预措施
iNKT cell loading dose:3x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：3x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: iNKT cells (Biological)
iNKT cell loading dose:3x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：3x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: IL-2 (Drug)
iNKT cell loading dose:3x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：3x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: Tegafur (Drug)
iNKT cell loading dose:6x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：6x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: iNKT cells (Biological)
iNKT cell loading dose:6x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：6x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: IL-2 (Drug)
iNKT cell loading dose:6x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：6x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: Tegafur (Drug)
iNKT cell loading dose:9x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：9x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: iNKT cells (Biological)
iNKT cell loading dose:9x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：9x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: IL-2 (Drug)
iNKT cell loading dose:9x10^7/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：9x10^7/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: Tegafur (Drug)
iNKT cell loading dose:1x10^10/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：1x10^10/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: iNKT cells (Biological)
iNKT cell loading dose:1x10^10/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：1x10^10/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: IL-2 (Drug)
iNKT cell loading dose:1x10^10/m2
Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC.
iNKT Cell Loading Dose：1x10^10/m2.
IL-2: IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.
Tegafur: Tegafur will be given at a dose of 40~60 mg bis in die (BID) 2 weeks.
干预措施: Tegafur (Drug)
结局指标
主要结局
Number of Adverse Events
时间窗: During the first 12 weeks, participants were assessed for adverse events every 2-4 weeks after infusion; after the first 12 weeks, participants were assessed for adverse events every 3 months, up to 20 months.
Defined as signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2.
次要结局
- Progression-Free Survival (PFS)(Through study completion, an average of 12 months.)
- Number of Participants With Stabilized (SD) or Progressive (PD) Disease.(4 weeks, 8 weeks, 12 weeks and 24 weeks after cell infusion.)
- Overall Survival (OS)(Through study completion, up to 20 months.)
研究者
LU JUN
Director of Hepatology and Cancer Biotherapy Ward
Beijing YouAn Hospital