This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-CD19 CAR-T cells in the treatment of patients with Multi-drug resistant SRNS
At present, there is no effective treatment for Multi-drug resistant steroid resistant nephrotic syndrome (MDR-SRNS), which has a high risk of progression to kidney failure, and about 55% of patients will have disease recurrence after receiving kidney transplantation, which is in urgent need of new treatment methods. CAR-T therapy is an adoptive cell therapy that uses genetic modification technology to reprogram T cells and eliminate target cells expressing disease-related antigens through antigen-specific recognition.Since 2019, CAR-T cell therapy has been successfully applied to autoimmune diseases. Although no clinical data related to CAR-T treatment of nephrotic syndrome has been disclosed, CAR-T is effective for systemic lupus erythematosus and systemic sclerosis.Many kinds of autoimmune diseases such as chemical syndrome and idiopathic inflammatory dermatomyositis have good therapeutic effect. These results suggest that the therapeutic effect of CAR T cells may not be limited to systemic lupus erythematosus, but may also play a role in several different B-cell-mediated and autoantibody-driven human autoimmune diseases, which is expected to bring breakthroughs in the treatment of MDR-SRNS.The purpose of this study is to assess the safety and efficacy of the anti-CD19 CAR-T cells in the treatment of patients with MDR-SRNS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Three dose groups (0.3×105/kg, 1×105/kg, 3×105/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.
Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGThe safety of CAR-T cell therapy in patients with MDR SRNS
Incidence and severity of Adverse Events (AEs) and Serious Adverse Event(SAEs),including changes in laboratory values,Electrocardiograph(ECG) and vital signs assessed by CommonTerminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: 3 months
The efficiency of CAR-T cell therapy in patients with MDR SRNS
Complete response and partial response rate (complete response defined as Urinary protein/creatinine ratio (uPCR) ≤200 mg/g for 3 consecutive days, partial response is defined as a 50% or more reduction in proteinuria from baseline and 200mg/g \< uPCR \<2000mg/g)
Time frame: 3 months
Effectiveness of other visit points
Rate of complete or partial response at other visit points after cell infusion (1 month, 2 months, 6 months, 9 months, 12 months, 18 months, 24 months)
Time frame: 24 months
Pharmacokinetic Outcome Cmax
The highest concentration (Cmax) of targeted CD19 CAR-T cells expanded in peripheral blood after infusion
Time frame: 3 months
Pharmacokinetic Outcome Tmax
The time to reach the maximum concentration (Tmax)
Time frame: 3 months
Pharmacokinetic Outcome AUC
The area under the curve (AUC) at 28 days and 90 days post-infusion (AUC28d/90d)
Time frame: 3 months
Pharmacodynamics Outcome
The degree of B cell clearance at various time points, and the concentration levels of CAR-T related serum cytokines such as IL-6, CRP, etc
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Time frame: 3 months