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

Plain-language summary

This single-center, prospective, exploratory Phase 1 trial examines CD19 CAR-T cell therapy for refractory membranous nephropathy. On top of standard symptomatic and supportive care, patients receive lymphodepleting chemotherapy with cyclophosphamide (fludarabine added if needed) plus prophylactic antihistamines and acetaminophen, followed by an infusion of CD19 CAR-T cells at 1x10^6 cells/kg, then two weeks of inpatient monitoring for vital signs and adverse reactions. Participants must have biopsy-confirmed primary membranous nephropathy classified as moderate- or high-risk refractory disease; planned follow-up is 1 year.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Recruiting

Sponsor

The First Affiliated Hospital of Air Force Medicial University

Intervention

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

Start date

12/8/2025

Estimated completion

7/31/2028

Countries

China

Related genes

Locations

• Xi'an, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.