Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of patients with adverse events.
研究概览
简要总结
Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy. Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients.
详细描述
CD19 single chain antibody-based chimeric antigen receptor (CAR)-engineered T cells have demonstrated great clinical potential in treating chronic and acute B cell leukemias. B cell lymphomas, similar to B cell leukemias, express CD19 surface molecules, and the majority of the B cell lymphoma patients cannot be cured by standard chemo-radiotherapy. CD19 CAR-based adoptive T cell therapy is associated with an unwanted adverse effect, the loss of CD19 B cells, which results in humoral immune deficiency. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal genetic mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients. The 4th generation design of the CAR incorporates the intracellular signaling domain of cluster of differentiation antigen 27 (CD27), known to be associated with T cell activation, survival and longevity. The inducible caspase 9 self-withdrawal design allows for rapid elimination of the infused CAR T cells upon complete eradication of the tumor cells, which will be followed by the recovery of humoral immunity. Patients receiving the 19273-4SCAR T cells will be closely monitored for infusion response, tumor eradication effect, longevity of the CAR T cells, and the recovery of B cell functions after withdrawal of the CAR T cells.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed or refractory CD19(+) B cell lymphoma patients proved by immuno-histochemistry (IHC) or Flow-cytometry.
- •Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Pulse oximetry of > 90% on room air.
- •Adequate hepatic function, defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN), aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.
- •Adequate renal function, defined as serum creatinine <2.0mg/dl.
- •Adequate heart function with LVEF≥50%
- •Measurable disease can be identified.
- •Life expectancy ≥3 months.
- •Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 1 year after the study is concluded. The male partner should use a condom.
- •Patients must sign an informed consent.
排除标准
- •Uncontrolled active infection.
- •Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).
- •HIV positive
- •Pregnant or lactating.
- •Currently enrolled in another clinical trial.
- •Concurrent use of systemic steroids.
结局指标
主要结局
Number of patients with adverse events.
时间窗: 2 years.
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
次要结局
- Survival time of the patients.(2 years.)
- Survival time of Anti-CD19 CAR T cells in vivo.(2 years.)
- Response rates to the 4th generation CAR T cells.(2 years.)
研究者
Jun Zhu
Director
Peking University