A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 200
- 试验地点
- 3
- 主要终点
- Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events
研究概览
简要总结
The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.
详细描述
Background:
T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Activation of T cell response from large tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying T cell costimulatory signals for CD28/CD27 plus an inducible apoptotic caspase 9 gene has been established. The study aims to evaluate the activities of a new CAR gene-modified T cells targeting CD19-positive tumors based on a CD19-specific single chain gene constructed 4SCAR (4SCAR19).
Objective:
To evaluate safety and efficacy of administrating 4SCAR19 T cells to patients with CD19 positive B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged more than 6 months.
- •malignant B cell surface expression CD19 molecules.
- •the KPS score over 80 points, and survival time is more than 3 months.
- •greater Hgb 80 g/L.
- •no contraindications to solid and cell separation
排除标准
- •accompanied with other active diseases, the treatment is difficult to correct.
- •bacteria, fungus, or virus infection, unable to control.
- •people living with HIV.
- •active HBV and HCV infection.
- •of pregnancy and nursing mothers.
- •before entering the test of the use of glucocorticoid systemic treatment within a week.
- •confirmed before used CAR - but invalid
研究组 & 干预措施
Therapeutic 4SCAR19 cells
Patients who have relapsed and refractory B cell leukemia after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells.
干预措施: Therapeutic 4SCAR19 cells (Genetic)
结局指标
主要结局
Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events
时间窗: 24 weeks
physiological parameter (for safety, measuring cytokine response, fever, symptoms)
次要结局
- Anti tumor activity of fourth generation anti CD19 CAR-T cells in patients with relapsed or refractory B cell malignancies(1 year)
研究者
Lung-Ji Chang
President
Shenzhen Geno-Immune Medical Institute