Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The proportion of subjects with DLT
研究概览
简要总结
This is a phase I, single arm, non-randomized, open label, treatment study trial to determine the recommended phase II dose of GC012F injection (CD19-BCMA CAR-T cells) in patients with refractory systemic lupus erythematosus.
详细描述
Systemic lupus erythematosus (SLE) is a kind of autoimmune diseases mediated by autoantibody-forming immune complexes, which involving multiple systems and organs.
Autoreactive B cells can self-activate and differentiate into plasma cells releasing large amounts of autoantibodies, while they can also present their own antigens to autoimmune T cells, thus activating T cells and promoting the release of inflammatory factors.
Traditional SLE treatment aims at long-term remission, while, CD19- BCMA CAR-T cells can theoretically completely deplete abnormal antibody-producing B cells, allowing immune rebuilding and restoring the patient's normal immune function, achieving drug-free survival, which fully reflects the application prospects of CAR-T therapy in SLE.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-70 years old;
- •Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;
- •SELENA-SLEDAI≥8;
- •Patients with CD19+ B-cell;
- •Active organ involvement;
- •Hemoglobin≥85 g/L;
- •WBC≥2.5×10^9/L
- •NEUT≥1×10^9/L;
- •PLT≥50×10^9/L;
- •AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%;
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis;
- •Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline. Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion.
- •Agree to attend follow-up visits as required;
- •Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative;
排除标准
- •Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L) within 8 weeks prior to leukapheresis, or subjects who need prohibited drugs to treat active nephritis or subjects who need hemodialysis;
- •CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts;
- •Patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system;
- •Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;
- •Received immunosuppressive therapy within 1 week prior to leukapheresis;
- •Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus; Patients with syphilis infection;
- •The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening;
- •Received live vaccine treatment within 4 weeks prior to screening;
- •Severe allergies or hypersensitivity;
- •Contraindication to cyclophosphamide in combination with fludarabine;
- •Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion;
- •cannula or drainage tubes other than central venous catheters;
- •Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;
- •Subjects with prior CD19 or BCMA-targeted therapy
- •Participated in any clinical study within 3 months prior to enrollment
- •Any situations that the investigator believes the patients are not suitable for the study.
研究组 & 干预措施
GC012F injection (CD19-BCMA CAR-T cells)
Dose level： DL1：1±20%×10^5/kg, DL2：2±20%×10^5/kg DL3：3±20%×10^5/kg
干预措施: GC012F injection (Drug)
结局指标
主要结局
The proportion of subjects with DLT
时间窗: Within 28 days after GC012F injection infusion
DLT definition is dose-limiting toxicity
The proportion of subjects with adverse events
时间窗: Within 12 weeks after GC012F injection infusion
All adverse events were evaluated according to NCI-CTCAE v5.0 criteria
次要结局
- Proportion of subjects achieving SRI-4(4, 8, 12 and 24 weeks after GC012F injection infusion)
- Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable)(After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24])
研究者
He Huang
Professor
Zhejiang University