A Phase I/II Study of Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 Chimeric Antigen Receptor T-Cells in Patients With Refractory CD19+ B-lineage Leukemia/Lymphoma
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
- Safety (incidence of adverse events defined as dose-limited toxicity)
研究概览
简要总结
This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.
详细描述
Primary objectives
- To determine the safety and feasibility of adoptive transfer of T cells modified to express CD19-specific chimeric antigen receptor (CD19CAR) for treatment of leukemia and lymphoma
Secondary objectives
- To measure the efficacy of anti-tumor responses after CD19CAR T cell infusion
- To determine if CD19CAR T cells engineered with 4-1BB signaling domain is superior to that with CD28 signaling domain for their homing and persistence after CD19CAR T cell infusion
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
- 5 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •5 Years to 70 Years, Male and female;
- •Expected survival > 12 weeks;
- •Performance score 0-2;
- •Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;
- •Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
- •Disease recurrence after stem cell transplantation;
- •Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
- •Creatinine < 2.5 mg/dl;
- •ALT/AST < 3x normal;
- •Bilirubin < 2.0 mg/dl;
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis;
- •Take contraceptive measures before recruit to this trial;
- •Written voluntary informed consent is given.
排除标准
- •Patients with symptoms of central nervous system
- •Accompanied by other malignant tumor
- •Active hepatitis B or C, HIV infection
- •Any other diseases could affect the outcome of this trial
- •Suffering severe cardiovascular or respiratory disease
- •Poorly controlled hypertension
- •A history of mental illness and poorly controlled
- •Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
- •Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
- •Reaching a steady dose if receiving anticoagulant therapy before assignment
- •Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- •Pregnant or lactating women
- •Subject suffering disease affects the understanding of informed consent or comply with study protocol.
研究组 & 干预措施
Mixed CD19CAR transfer
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
干预措施: anti-CD19 CAR-T (Biological)
Mixed CD19CAR transfer
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
干预措施: Fludarabine (Drug)
Mixed CD19CAR transfer
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Safety (incidence of adverse events defined as dose-limited toxicity)
时间窗: 30 days
次要结局
- Overall complete remission rate(8 weeks)
- Survival of CAR T cells in circulation measured by flow cytometry and PCR(1 year)
- Overall survival(1 year)
- Duration of remission(1 year)
研究者
Chengzhi
Director of Department of Hematology
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine