Dirençli Membranöz Nefropati Tedavisinde CD19 Kimerik Antijen Reseptörü T Hücresinin (CAR-T) Güvenliği ve Etkinliği

Sade dilde özet

Bu tek merkezli, ileriye dönük Faz 1 (Phase 1) çalışma, dirençli membranöz nefropatide (refractory membranous nephropathy) CD19 hedefli CAR-T hücre tedavisini inceliyor. Hastalara standart destek tedavisinin yanı sıra, siklofosfamid (gerekirse fludarabin eklenerek) ile lenfosit azaltıcı kemoterapi ve koruyucu ilaç uygulamasının ardından kilogram başına 1x10^6 hücre dozunda CD19 CAR-T infüzyonu yapılıyor; sonraki 2 hafta boyunca hastalar yaşamsal bulgular ve yan etkiler açısından hastanede izleniyor. Katılımcıların böbrek biyopsisiyle doğrulanmış birincil membranöz nefropati tanısı ve orta ya da yüksek riskli dirençli hastalık sınıflaması bulunmalıdır; planlanan takip süresi 1 yıldır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Faz 1 (Phase 1)

Durum

Katılımcı alıyor

Sponsor

The First Affiliated Hospital of Air Force Medicial University

Müdahale

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

Başlangıç

08.12.2025

Tahmini bitiş

31.07.2028

Ülkeler

China

İlgili genler

Merkezler

• Xi'an, China

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

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.