A Study of CD19/CD20 Dual CAR-T Cells in the Treatment of Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma(B-NHL)
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Objective remission rate(ORR)
研究概览
简要总结
This is a single center, single arm, open-label, phase I study to evaluate the safety and efficacy of CD19/CD20 Dual-CAR-T cells in patients with refractory or relapsed B-NHL.
详细描述
This Phase I study is designed as a pilot trial evaluating the safety and efficacy of CD19/CD20 Dual-CAR-T cell therapy in subjects with refractory and relapsed B-NHL. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of CD19/CD20 Dual-CAR-T cells. Safety and efficacy of CD19/CD20 Dual-CAR-T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19/CD20 Dual-CAR-T cells therapy in patients with refractory and relapsed 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
- 1 Year 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •NHL confirmed by cytology or histology, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, etc.
- •Relapse or refractory after at least second-line treatment;
- •With evaluable target lesions.Measurable target lesions: lymph nodes>1.5x1.0cm, extranodal lesions>1.0x1.0cm;
- •Double positive expression of CD19 / CD20 in B cells;
- •ECOG score 0-2 points;
- •Good organ function:
- •Blood routine: absolute neutrophil count (ANC) ≥1.0×109/L; hemoglobin (Hb) ≥80 g/L; platelet count (PLT) ≥50×109/L; Blood biochemistry: total bilirubin≤3×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤3×upper limit of normal (ULN); Pulmonary function: ≤CTCAE Grade 1 dyspnea and SaO2≥92% in indoor air environment; Heart function: Left ventricular ejection fraction (LVEF) ≥50%.
- •Women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside;
- •Patients who voluntarily sign informed consent and are willing to comply with treatment plans.
排除标准
- •Active infections that are difficult to control;
- •Active hepatitis B, active hepatitis C, human immunodeficiency virus (HIV) antibody positive, and Treponema pallidum antibody test positive;
- •The tumor invades the central nervous system or primary CNS lymphoma;
- •Anti-GVHD (acute or chronic) treatment is being performed within 4 weeks before apheresis and cell infusion;
- •Have undergone the following treatments:
- •Those who have received chemotherapy or radiotherapy 5 days before apheresis;
- •Those who have used drugs that stimulate the production of bone marrow hematopoietic cells within 5 days before apheresis;
- •Received donor lymphocyte infusion (DLI) within 6 weeks before cell infusion;
- •Have received autologous hematopoietic stem cell transplantation (HSCT) 3 months before apheresis, or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 12 months;
- •Have used any gene therapy products before;
- •History of epilepsy or other central nervous system diseases; or clinically diagnosed as having severe thyroid dysfunction; or active autoimmune diseases;
- •History of other malignant tumors that have not been remission for at least 3 years ;
- •Any of the following cardiovascular diseases occurred within 6 months of the screening period, including NYHA heart function grade III or IV heart failure, cardiovascular angioplasty or stent, myocardial infarction, unstable angina, or other clinical symptoms Significant heart disease;
- •Pregnant or lactating women;
- •The investigator believes that there are other factors that are not suitable for selection or that affect subjects' participation or completion of the study.
研究组 & 干预措施
CD19/CD20 Dual-CAR-T cells
CD19/CD20 Dual-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest for at least 2 days before infusion.
干预措施: CD19/CD20 Dual-CAR-T cells (Biological)
结局指标
主要结局
Objective remission rate(ORR)
时间窗: 6 months
The percentage of participants who achieved complete remission (CR) and partial remission over all participants.
Percentage of adverse events
时间窗: 6months
Percentage of participants with adverse events.
次要结局
- Relapse-Free Survival(RFS )(6 months)
- Overall-Survival(OS)(6 months)