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Safety and Efficacy of CD19 Chimeric Antigen Receptor T-Cell (CAR-T) in the Treatment of Refractory Membranous Nephropathy

RecruitingPhase 1Ages 18 Years - anyAllThe First Affiliated Hospital of Air Force Medici…
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In plain words

What the trial is, and whether it could suit you

This study is a single-center, prospective, exploratory Phase I clinical trial initiated by the team led by Associate Professor He Lijie from the Department of Nephrology, Xijing Hospital. Prior to receiving CAR-T cell therapy, patients will undergo lymphodepletion chemotherapy with cyclophosphamide (fludarabine will be added if necessary). After prophylactic administration of antihistamines and acetaminophen, patients will be infused with CD19 CAR-T cells at a dose of 1×10⁶ cells/kg. In the subsequent 2 weeks, patients will be hospitalized for monitoring of vital signs and adverse reactions. The planned follow-up duration of this study is 1 years.

Sign in to get the eligibility rules as simple questions to take to your doctor.

📋 Eligibility rules (as published)
Inclusion Criteria: * Confirmed as primary membranous nephropathy (PMN) by renal biopsy. * Classified as moderate-risk or high-risk refractory membranous nephropathy (rMN). * Moderate-risk rMN is defined as: eGFR ≥ 90 ml/min/1.73m² AND 24-hour urinary protein \> 3.5g/d, with a reduction of no more than 50% within 6 months of receiving renin-angiotensin system inhibitor (RASi) therapy. * High-risk rMN is defined as meeting one of the following: 1. eGFR \< 60 ml/min/1.73m² and/or persistent proteinuria \> 8g/d for more than 6 months. 2. Normal eGFR with proteinuria \> 3.5g/d and ≤50% reduction after 6 months of RASi therapy, PLUS at least one of the following: Serum albumin \< 25g/L; PLA2R antibody \> 50 RU/mL; Urinary α1-microglobulin \> 40 μg/min; Urinary IgG \> 1 μg/min; Urinary β2-microglobulin \> 250 mg/d; IgG/albumin clearance ratio \> 0.20. * Diagnosis of rMN requires failure of adequate first-line immunosuppressive therapy (≥6 months of steroids+cyclophosphamide, CNI, or rituximab), defined by any of the following: persistent high-titer anti-PLA2R antibody; for antibody-negative patients, persistent nephrotic syndrome (protein \>3.5g/d, albumin \<30g/L); \<50% reduction in proteinuria. * Age ≥ 18 years. * Adequate organ function, defined as: 1. Renal: eGFR ≥ 30 ml/min/1.73m². 2. Hepatic: ALT and AST ≤ 2.5 x ULN; Total bilirubin ≤ 1.5 x ULN. 3. Cardiac: LVEF ≥ 50%; NYHA Class I or II; No significant arrhythmias requiring intervention; No major cardiovascular events within the past 6 months. 4. Respiratory: SpO2 \> 92% on room air. * Ability to understand and willingness to sign an Informed Consent Form. Exclusion Criteria: * Secondary membranous nephropathy (e.g., due to SLE, malignancy, drugs, infection). * Active infection requiring IV antibiotics, active tuberculosis, or positive viral serology indicating active infection, including: 1. HBV: HBsAg (+) and/or HBcAb (+) with detectable HBV DNA. 2. HCV: HCV Ab (+) with detectable HCV RNA. 3. HIV Ab (+). 4. Active EBV or CMV infection (IgM+ or DNA above normal). 5. Positive syphilis (Treponema pallidum) antibody (requires evaluation for active infection). * Severe uncontrolled comorbidities, including: 1. Uncontrolled hypertension (persistent SBP \> 160 mmHg or DBP \> 100 mmHg). 2. Uncontrolled diabetes (HbA1c \> 8% or random glucose ≥11.1 mmol/L) or diabetic nephropathy. 3. Symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months. 4. Active peptic ulcer or gastrointestinal bleeding within the past 6 months. 5. Severe congenital or acquired immunodeficiency. 6. Severe CNS diseases (e.g., catastrophic APS, uncontrolled epilepsy). 7. End-stage organ failure not attributable to PMN. * History of malignancy within the past 5 years, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ, or thyroid cancer. * Specific treatment history or plans, including: 1. Prior receipt of any cell therapy (e.g., MSCs, HSCT). 2. Major surgery within 24 weeks before or planned within 24 weeks after enrollment. 3. Planned kidney transplantation within 3 years. 4. History of substance abuse. * Participation in another interventional clinical trial within 3 months prior to enrollment. * Pregnant or lactating women. * Inability to understand the study or provide informed consent (e.g., severe dementia, mental illness). * Any other condition deemed by the investigator to increase risk, interfere with assessment, or affect compliance.
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What it tests

  • All patients will receive CD19 CAR-T cell therapy on the basis of standard symptomatic and supportive treatment.
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Where

1 site
Department of Nephrology, Xijing Hospital
Xi'an, China
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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