A Study Evaluated Efficacy and Safety of CD19/22 Chimeric Antigen Receptor T Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19/22 CART cells combined with PD-1 Inhibitor in relapsed/refractory B Cell Lymphoma.
详细描述
Though response rates have greatly improved with the development of Chimeric antigen receptor T cells (CART) therapy in refractory/relapsed B cell non-Hodgkin's lymphoma (R/R B-NHL), the response can't usually last long and relapse occurs in a large proportion of patients who receive CART cells infusion. The main reasons of relapse might be tumor antigen loss and a lack of CART cell persistence. Currently, preclinical studies have shown that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. In parallel, the combined use of CART-19 and CART-22 cells has a better potential to reduce antigen escape and increase anti-tumor activity. Therefore, the combination of CD19/22 CART and PD-1 inhibitor is one of the ways to improve the therapeutic effect of CART cells. This study was conducted to explore the efficacy and safety of CD19/22 CART cells in R/R B-NHL.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •R/R B-NHL with measurable (≧1.5cm) lesions confirmed by pathological immunohistochemistry or flow cytometry ( meeting any of the following conditions):
- •A.The lesion shrinkage <50% or disease progression after 4 courses of standard first-line treatment or 2 courses of two-line treatment (primary refractory disease) B. Progress disease as the best response after hematopoietic stem cell transplantation C.Progress disease or stable disease as the best response to most recent therapy regimen
- •Age ≥ 18 years
- •The Eastern Cooperative Oncoloy Group (ECOG) physical condition score ≤ 2 points
- •The main organ functions need to meet the following conditions:
- •A.Left ventricular ejection fraction ≥50% B.Creatinine ≤132umol/l or creatinine clearance ≥60 ml/min C.ALT and AST≤2 upper limitation of normal D.SpO2 > 90%
- •Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion
- •Expected survival exceeds 3 months
- •Written informed consent could be acquired
排除标准
- •Immunosuppressant medications or steroids was used within 2 weeks before cell collection, or need to use steroids or immunosuppressant medications more than two years
- •Uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infection
- •Active hepatitis B or hepatitis C infection
- •HIV infection
- •Severe acute or chronic graft-versus-host disease (GVHD)
- •Participated in any other drug research clinical trials within 30 days before enrollment
- •Prior CART cells therapy within 3 months before enrollment
- •Prior allogeneic hematopoietic stem cell transplantation within 6 months before enrollment
- •Have contraindications to the PD-1 inhibitors
- •Uncontrolled other tumor
- •Women in pregnancy,lactation or planning to become pregnant
- •The researcher considers inappropriate to participate in this research
研究组 & 干预措施
CD19/22 CART cells combined with PD-1 inhibitors
Patients will receive PD-1 inhibitor on the first day after CART cell infusion
干预措施: CD19/22 CART (Biological)
CD19/22 CART cells combined with PD-1 inhibitors
Patients will receive PD-1 inhibitor on the first day after CART cell infusion
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 1 year
Number of patients who achieved response (complete response and partial response ) after treatment of CD19/22 CART combined with PD-1 inhibitor. Response will be assessed using the Lugano criteria.
Progression-free survival(PFS)
时间窗: 1 year
PFS will be assessed from the first CART cell infusion to progression,death or last follow-up.
次要结局
- Duration of overall response (DOR)(1 year)
- Overall survival(OS)(1 year)
- Incidence of treatment-related adverse events(1 year)
- Complete relapse rate(CR)(1 year)