Autologous CD19 Car T-Cell Therapy For Patients With Severe Refractory Systemic Lupus Erythematosus - A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Rate of Adverse events
研究概览
简要总结
This pilot clinical study aims to evaluate the effectiveness of Chimeric Antigen Receptor (CAR) T-cell therapy in treating severe, refractory systemic lupus erythematosus (SLE), an autoimmune disease driven by autoreactive B-cells. Current treatments for severe SLE, including glucocorticoids, cytotoxic, and immunosuppressive drugs, have significant limitations. These treatments do not adequately control the underlying autoimmune process and require long-term use, leading to chronic side effects and often failing to prevent permanent organ damage. Given the high prevalence and mortality rates associated with SLE in regions like Asia and Malaysia, there is a pressing need for more effective therapies.
详细描述
This study seeks to investigate CAR-T cell therapy's potential for treating severe treatment-refractory systemic lupus erythematosus (SLE) in Malaysian patients.
STUDY OBJECTIVES
General Objective: To evaluate the safety and efficacy of autologous CD19 CAR T-cell infusion in patients with severe refractory SLE.
Specific Objectives:
To evaluate the safety and tolerability of treatment. To evaluate efficacy as measured by response rates and survival. To evaluate the quality of life based on the use of validated health questionnaire tools.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between ≥ 18 to ≤ 65 years Clinical Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria (Fanouriakis et al., 2019) Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history Active disease (defined by not being in remission according to DORIS criteria or in a low disease activity state [LLDAS]) (Franklyn et al., 2016, van Vollenhoven et al., 2021) With at least one active organ system involvement Persistent active disease with insufficient response to glucocorticoids and at least 2 of the following treatments for at least 3 months each: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus or voclosporin.
- •Serum ALT <5 times the normal value, serum bilirubin <3 times the normal value, Left ventricular ejection fraction >45% Life expectancy of more than 3 months Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Psychological, sociological or geographical conditions precluding compliance A female of childbearing age must have a negative pregnancy test and is on two effective contraception methods A male must use two effective contraception methods
排除标准
- •Active cancer or receiving cancer treatment Evidence of severe lung, FVC <45% and/or DLCO (corrected for Hb) <30% predicted, heart (NYHA class III/IV, arrhythmia, AV block, uncontrolled hypertension), liver failure or severe neurologic disorders.
- •Pre-existing irreversible kidney damage and creatinine clearance below 30 ml/min ( to review) Severe pancytopenia HIV positivity. Active Hepatitis B, C infection. Septicemia. Pregnant/nursing female. Receiving stem cell transplant within 12 weeks of enrolment, chemotherapy or radiotherapy within 8 weeks of enrolment Active CNS involvement.
研究组 & 干预措施
autologous CD19 CAR T-cells
Single Infusion of autologous CD19 CAR T- cells
干预措施: CD19 CAR-T cells (Biological)
结局指标
主要结局
Rate of Adverse events
时间窗: Starting form day 0 up to 24 months after CAR-T cells infusion
Incidence of adverse event (AE), classified according to CTCAE version 5.0, and evaluation and classification of Cytokine Release Syndrome (CRS) and Immune Effector cell-associated Neurotoxicity Syndrome (ICANS)
SLEDAI Remission Rate
时间窗: Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion
Remission is evaluated by fulfilment of SLEDAI remission criteria
次要结局
- Clinical Response Rate(Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion)
- Rate of B cell aplasia(Months 1, 3, 6, 9, 12, 15, 18, 21, 24 after CAR-T cells infusion)
- Rate of Immunological response(Months 1, 3, 6, 9, 12, 15, 18, 21, 24 after CAR-T cells infusion)
- Mean of Quality of life score(Weeks 4, 8, 12, 16, 20, 24,28 after CAR-T cells infusion)