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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Incidence of DLT in rMN subjects after a single infusion of CD19 CAR-T cells [Срок оценки: 28 days and 3 months after infusion]
• Incidence of AE in rMN subjects after a single infusion of CD19 CAR-T cells [Срок оценки: 12 months after infusion]

Вторичные конечные точки (12)

• Overall response rate (CR+PR) in rMN subjects after cell infusion [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• Proportion of rMN subjects achieving CR after cell infusion [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• Proportion of rMN subjects achieving PR after cell infusion [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• rMN recurrence after cell infusion [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• eGFR [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• Urine protein [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• UACR [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• anti-PLA2R antibody [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• Scr, CysC [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• Routine blood test [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]
• CRP [Срок оценки: Day 2, Day 7, Day 10 or 14, Day 21, Day 28 (1 month) after infusion]
• Serum complements C3, C4 [Срок оценки: Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion]

Критерии участия

Критерии включения

• 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:

• eGFR < 60 ml/min/1.73m² and/or persistent proteinuria > 8g/d for more than 6 months.
• 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:

• Renal: eGFR ≥ 30 ml/min/1.73m².
• Hepatic: ALT and AST ≤ 2.5 x ULN; Total bilirubin ≤ 1.5 x ULN.
• Cardiac: LVEF ≥ 50%; NYHA Class I or II; No significant arrhythmias requiring intervention; No major cardiovascular events within the past 6 months.
• Respiratory: SpO2 > 92% on room air.
• Ability to understand and willingness to sign an Informed Consent Form.

Критерии исключения

• 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:

• HBV: HBsAg (+) and/or HBcAb (+) with detectable HBV DNA.
• HCV: HCV Ab (+) with detectable HCV RNA.
• HIV Ab (+).
• Active EBV or CMV infection (IgM+ or DNA above normal).
• Positive syphilis (Treponema pallidum) antibody (requires evaluation for active infection).
• Severe uncontrolled comorbidities, including:

• Uncontrolled hypertension (persistent SBP > 160 mmHg or DBP > 100 mmHg).
• Uncontrolled diabetes (HbA1c > 8% or random glucose ≥11.1 mmol/L) or diabetic nephropathy.
• Symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months.
• Active peptic ulcer or gastrointestinal bleeding within the past 6 months.
• Severe congenital or acquired immunodeficiency.
• Severe CNS diseases (e.g., catastrophic APS, uncontrolled epilepsy).
• 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:

• Prior receipt of any cell therapy (e.g., MSCs, HSCT).
• Major surgery within 24 weeks before or planned within 24 weeks after enrollment.
• Planned kidney transplantation within 3 years.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Nephrology, Xijing Hospital — Сиань

Идентификаторы

NCT: NCT07266181 · KY20252388-F-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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