Phase Ⅰ Study of CAR19 T Cells Carrying Cytoplasmic Activated PD-1 in the Treatment of Refractory/Relapsed B Cell Lymphoma
试验速览
- 阶段
- 1 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- safety: occurrence of study related adverse events
研究概览
简要总结
Evaluation of the safety and efficacy of CAR19 T cells carrying cytoplasmic activated PD1 in patients with refractory relapsed B-cell lymphoma
详细描述
Although CAR19 T cell therapy brings hope, the patients with refractory/relapsed B-cell lymphoma is still a problem for the current treatment. There are still some patients with poor therapeutic efficacy, and the efficacy of CAR19-T cell therapy remains to be improved. Basic research shows that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. However, the regimen of CAR19-T cells combined anti-PD1 inhibitors need to be combined with the application of anti-PD1 antibody and culture of CART cells during the treatment, there may be adverse events to PD1 antibodies. In this study, CAR19T cells carrying cytosolic activated PD1 possess the dual effects of CAR19T cells and anti-PD1 or anti-PD-L1 antibodies while overcoming the adverse events of anti-PD1 inhibitors, and might have better efficacy than conventional CAR19T cells plus anti-PD1 or anti-PD-L1 antibody treatment, with fewer side effects.
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 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
- •18-70 years old and the expected lifetime >3 months
- •Refractory/relapsed CD19 positive B cell lymphoma by pathology
- •ECOG score <2
- •Measureable lesions according to RECIST 1.1
- •Sufficient heart, liver, kidney and bone marrow function (heart: no heart disease or coronary heart disease, patient heart function NYHA grade 1-2; liver: TBIL ≤ 3ULN, AST ≤ 2.5ULN, ALT ≤ 2.5ULN; kidney: Cr≤ 1.25ULN; bone marrow: WBC ≥ 2.0 × 109/L, Hb ≥ 80 g/L, PLT ≥ 30 × 109/L)
- •no serious allergies
- •No other serious diseases that conflict with this protocol (eg, autoimmune diseases, immunodeficiency, organ transplantation)
- •No other history of malignancy
- •No serious mental disorders
- •Women of childbearing age must be negative for blood pregnancy test within 7 days and must take appropriated contraceptive measures during and 3 months after the study
- •The patient himself agrees to participate in this clinical study and signed the "informed consent"
排除标准
- •Lactating women
- •Severe infectious or viral diseases (HIV positive, syphilis, etc.)
- •Active hepatitis B or C viral hepatitis
- •Patients who used high-dose glucocorticoids within 1 week
- •Participation in other clinical studies in the past 3 months or having been treated with other gene products
研究组 & 干预措施
CAR19 T cells carrying cytoplasmic activated PD-1
patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells.
干预措施: CAR19 T cells carrying cytoplasmic activated PD-1 (Drug)
结局指标
主要结局
safety: occurrence of study related adverse events
时间窗: 6 months
occurrence of study related adverse events
次要结局
- objective response rate(3 months and 6 months)