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RecruitingPhase 1NCT07266181

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

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

Sponsor

The First Affiliated Hospital of Air Force Medicial University

Enrollment

5 participants

Start Date

Dec 8, 2025

Study Type

INTERVENTIONAL

Conditions

Refractory Membranous Nephropathy

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria14

  • 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.

Exclusion Criteria25

  • 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.

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Interventions

OTHERAll 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.

Locations(1)

Department of Nephrology, Xijing Hospital

Xi'an, China, China

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NCT07266181