Clinical Trial for the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Systemic Lupus Erythematosus
详细描述
Autoimmune diseases only show local pathological damage, but more often systemic lesions. If not diagnosed and treated in time or poorly controlled, a risk of disability or even death as the course of the disease progresses. Studies have shown that B cells can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or they can differentiate into plasma cells to release autoantibodies, and play an important role in the occurrence and progression of autoimmune diseases. In recent years, it has become a major research focus to deplete B cells in patients or inhibit B cell function. This research focuses on CAR-T cells killing B cells. In 2019, Kansal and others released their team's in vivo experiments to prove that CD19 CAR-T cells have achieved significant and long-lasting effects in the treatment of systemic lupus erythematosus. This fully reflects the application prospects of CAR-T cells in autoimmune diseases.
Based on the current research progress, our center intends to conduct research on the safety and effectiveness of CD19/BCMA CAR-T cells in the treatment of refractory systemic lupus erythematosus.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Systemic lupus erythematosus with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment
- •Estimated survival time> 12 weeks;
- •Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up;
- •Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
排除标准
- •Subjects with any of the following exclusion criteria were not eligible for this trial:
- •History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
- •Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
- •Pregnant (or lactating) women;
- •Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
- •Active infection of hepatitis B virus or hepatitis C virus;
- •Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
- •Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
- •Other uncontrolled diseases that were not suitable for this trial;
- •Patients with HIV infection;
- •Any situations that the investigator believes may increase the risk of patients or interfere with the results of study
- •Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L
- •Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: Baseline up to 28 days after CD19/BCMA CAR T-cells infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 90 days after CD19/BCMA CAR T-cells infusion
Incidence of treatment-emergent adverse events \[Safety and Tolerability\]
次要结局
- Autoantibody detection(Up to 90 days after CD19/BCMA CAR T-cells infusion)
- Concentration of CAR-T cells(From admission to the end of the follow-up, up to 2 years)
- Objective Response Rate, ORR(In 3 months of CD19/BCMA CAR-T cell infusion)
- Disease control rate, DCR(From Day 28 CD19/BCMA CAR-T infusion up to 2 years)
- Duration of remission, DOR(24 months post CD19/BCMA CAR-T cells infusion)
- Progression-free survival, PFS(24 months post CD19/BCMA CAR-Tcells infusion)
- Overall survival, OS(From CD19/BCMA CAR-T infusion to death，up to 2 years)
研究者
He Huang
Clinical Professor
Zhejiang University