An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Safety of CAR-T cell（i.v.）by number of patients with adverse event
研究概览
简要总结
CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of the central nervous system). SLE is a kind of autoimmune diseases which involving multiple systems, organs and with the present of a variety of autoantibodies. In the conventional treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells in the treatment of SLE.
详细描述
This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of systemic lupus erythematosus (SLE) patients
- •Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry
- •Age: 18-69 years old
- •Creatinine < 1.5 mg/dl
- •cardiac ejection fraction>55%
- •hemoglobin>9g/dL
- •Bilirubin <2.0 mg/dl
- •Successful test expansion of T-cells
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis
- •Voluntary informed consent is given
排除标准
- •Pregnant or lactating women
- •Uncontrolled active infection
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- •Previously treatment with any gene therapy products
- •Feasibility assessment during screening demonstrates<5% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
- •Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, serious arrhythmia)
研究组 & 干预措施
Reduce B cells
Patients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity.
干预措施: cyclophosphamide (Drug)
Treatment of SLE
Patients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE.
干预措施: anti-CD19-CAR-T cells (Drug)
结局指标
主要结局
Safety of CAR-T cell（i.v.）by number of patients with adverse event
时间窗: 6 weeks
adverse event is evaluated with CTCAE, version 4.0
次要结局
- 3. Detection of transferred T cells in the circulation using quantitative -PCR(6 weeks)
- Number of patients with tumor response(8 weeks)