CD19 CAR-T Therapy for Refractory Childhood-Onset Systemic Lupus Erythematosus
A Clinical Study of CD19 Chimeric Antigen Receptor T-Cell Therapy for Patients With Refractory Childhood-Onset Systemic Lupus Erythematosus
This study is evaluating the safety and potential benefits of CD19 chimeric antigen receptor T-cell (CAR-T) therapy in children and young adults with severe systemic lupus erythematosus (SLE) that began during childhood. The study will include up to 8 participants aged 25 years or younger whose disease remains active despite treatment with multiple immune-suppressing medicines and has affected at least one major organ.
CAR-T cells will be made from each participant's own T cells and modified to recognize CD19, a protein found on B cells that contribute to SLE. Participants will receive chemotherapy to reduce existing immune cells, followed by a single intravenous infusion of SNUH-CD19-CAR-T cells. They will be monitored for side effects and changes in disease activity, organ involvement, laboratory findings, and the need for steroids or other immune-suppressing medicines. The main assessment will be performed 1 year after the CAR-T cell infusion.
研究概览
地位
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习联系方式
- 姓名：Hye Ji, CRC
- 电话号码：82-10-2957-8895
- 邮箱：hyeji91@snu.ac.kr
学习地点
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Seoul、韩国
- 招聘中
- Seoul National University Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
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Participants must be 25 years of age or younger at the time of SNUH-CD19-CAR-T infusion.
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Participants must have a diagnosis of systemic lupus erythematosus and meet the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for systemic lupus erythematosus.
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Participants must be currently receiving or have previously received at least three of the following therapies, including corticosteroids: hydroxychloroquine, methotrexate, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, rituximab, or belimumab.
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Participants must have involvement of at least one of the following major organ systems:
- Kidney: class II-V lupus nephritis confirmed by biopsy or proteinuria greater than 0.5 g/day
- Heart: pericarditis, myocarditis, conduction abnormality, or valvular disease
- Lung: pleuritis, interstitial lung disease, or pulmonary arterial hypertension
- Hematologic system: platelet count below 50,000/μL or hemolytic anemia
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Participants must have uncontrolled active disease, defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 10 or higher.
Exclusion Criteria:
- Severe active central nervous system lupus requiring current treatment, including uncontrolled seizures, psychotic symptoms, or cognitive impairment.
- Inability to obtain an adequate leukapheresis product suitable for the manufacture of SNUH-CD19-CAR-T cells.
- Known human immunodeficiency virus infection.
- Uncontrolled active infection, as determined by the investigator. An infection will be considered controlled if appropriate treatment has been administered and there is no evidence of progression at enrollment. Persistent fever without other signs or symptoms of infection will not, by itself, be considered evidence of progressive infection.
- Pregnancy or breastfeeding.
- Any medical or other condition that, in the investigator's clinical judgment, makes participation in the study inappropriate.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：SNUH-CD19-CAR-T Treatment
Participants will receive protocol-defined lymphodepleting chemotherapy followed by a single intravenous infusion of autologous SNUH-CD19-CAR-T cells at a dose of 0.2 to 1.0 × 10^6 CAR-positive viable T cells/kg. |
Autologous T cells genetically modified to express a CD19-targeted chimeric antigen receptor. Participants will receive a single intravenous infusion at a dose of 0.2 to 1.0 × 10^6 CAR-positive viable T cells/kg. Participants will receive protocol-defined lymphodepleting chemotherapy before CAR-T cell infusion. The preferred regimen consists of intravenous fludarabine 30 mg/m²/day for 4 days and cyclophosphamide 500 mg/m²/day for 2 days. Alternative regimens, dose reduction, partial administration, or omission may be used according to the protocol and the investigator's clinical judgment |
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
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Proportion of Participants Achieving Lupus Low Disease Activity State
大体时间：1 year after SNUH-CD19-CAR-T infusion
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1 year after SNUH-CD19-CAR-T infusion
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Proportion of Participants With Lupus Nephritis Achieving a Renal Response
大体时间：1 year after SNUH-CD19-CAR-T infusion
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Among participants with lupus nephritis at baseline, renal response is defined as achievement of either a complete or partial renal response according to protocol-specified criteria. Complete renal response requires eGFR ≥90 mL/min/1.73 m² or ≥90% of baseline, urine protein-to-creatinine ratio <0.5 g/g, normal or inactive urinary sediment, and normal serum creatinine or a value within 15% of baseline. Partial renal response requires eGFR ≥80% of baseline or an improvement of ≥25%, a ≥50% reduction in urine protein-to-creatinine ratio to <3.0 g/g, and serum creatinine ≤125% of baseline. |
1 year after SNUH-CD19-CAR-T infusion
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合作者和调查者
出版物和有用的链接
一般刊物
- Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
- Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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