CD19 CAR-T therapy for refractory primary membranous nephropathy

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

This will try CD19 CAR-T cell therapy in people with primary membranous nephropathy that has not responded to standard immunosuppressive treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Air Force Medicial University (Academic / other)
• Drugs / interventions: rituximab, cyclophosphamide, CAR-T, chemotherapy, fludarabine
• Locations: 1 site (Xi'an, China)
• Trial ID: NCT07266181 on ClinicalTrials.gov

What this trial studies

This single-center, prospective Phase I trial tests the safety and preliminary efficacy of CD19 CAR-T cells in refractory primary membranous nephropathy. Participants receive lymphodepletion with cyclophosphamide (with fludarabine added if needed), followed by prophylaxis with antihistamines and acetaminophen and a single infusion of CD19 CAR-T cells at 1 × 10^6 cells/kg. Patients are hospitalized for about two weeks for close monitoring of vital signs and adverse reactions and are followed for one year to track kidney function, proteinuria, and immune markers. The trial is exploratory and is primarily focused on safety with secondary observations of clinical and serologic responses.

Who should consider this trial

Good fit: Ideal candidates are people with biopsy-proven primary membranous nephropathy classified as moderate- or high-risk refractory disease who have failed adequate first-line immunosuppressive therapy.

Not a fit: Patients with secondary membranous nephropathy, those who have not yet failed standard immunosuppressive options, or those with active serious infections or significant comorbidities are unlikely to benefit from this experimental therapy.

Why it matters

Potential benefit: If successful, this approach could eliminate pathogenic B cells and antibodies, potentially inducing remission and reducing proteinuria in patients with refractory membranous nephropathy.

How similar studies have performed: CD19-targeted CAR-T is an emerging strategy in autoimmune disease with limited case reports and early-phase work showing promise, but its application to membranous nephropathy remains largely experimental.

Eligibility criteria

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.

Where this trial is running

Xi'an, China

• Department of Nephrology, Xijing Hospital — Xi'an, China, China (Recruiting)

Study contacts

• Study coordinator: Jipeng Li

Conditions Refractory Membranous Nephropathy