Adoptive Immunotherapy for HLA_A2 Genotype gp100 Positive Malignant Melanoma With GPA-TriMAR-T Cell
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
研究概览
简要总结
Malignant melanoma have been reported to be characterized with high gp100 expression. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the GPA-TriMAR-T cells will recognize and kill target cells that express gp100(209-217) peptides in the form MHC-I complex, thus eliminating malignant melanoma from the body.
详细描述
GPA-TriMAR is a modified chimeric antigen receptor (CAR) that consist of three subunit in it's outer membrane domain. The outer membrane domain linked to the inner membrane 4-1BB/CD3ζ domain through the transmembrane domain, thus compose the complete chimeric antigen receptor. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the modified GPA-TriMAR-T cells will recognize and kill malignant melanoma cells in the body, and in the meanwhile the other two subunits function to stimulate the innate immune system and enhance GPA-TriMAR-T cells tumor Infiltration.
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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
- •All subjects must be able to comply with all the scheduled procedures in the study;
- •HLA_A2 genotype and gp100 positive malignant melanoma： Ⅳ stage or relapsed after surgery or chemotherapy or no available standard therapy;
- •At least one measurable lesion per RECIST V1.1;
- •Aged 18 to 69 years;
- •Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2;
- •Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
- •All other treatment induced adverse events must have been resolved to ≤grade 1;
- •Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB>70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);
排除标准
- •Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment);
- •Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;
- •Lactating women or women of childbearing age who plan to conceive during the time period;
- •Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
- •Known history of infection with HIV;
- •Subjects need systematic usage of corticosteroid;
- •Subjects need systematic usage of immunosuppressive drug;
- •Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
- •Other reasons the investigator consider the patient may not be suitable for the study.
结局指标
主要结局
safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
时间窗: 24 months
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
次要结局
- Complete response rate[CR] （Complete response rate per the revised International Working Group (IWG) Response Criteria）(24 months)
- Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）(24 months)
- Duration of Response （The time from response to relapse or progression）(24 months)
- Progression Free Survival （The time from the first day of treatment to the date on which disease progresses.）(24 months)
- Overall Survival （The number of patient alive, with or without signs of cancer）(24 months)