Clinical Study of Anti-CD19/BCMA Universal Chimeric Antigen Receptor T Cells (UCAR-T) in the Treatment of Refractory Idiopathic Membranous Nephropathy (IMN)

Обзор

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19/BCMA Universal Chimeric Antigen Receptor T Cells (UCAR-T) in the Treatment of Refractory Idiopathic Membranous Nephropathy (IMN)

Вмешательства

• Препарат CD19/BCMA-Targeted Universal Chimeric Antigen Receptor T Cells (UCAR-T) infusing
  Patients will receive Fludarabine and Cyclophosphamide on day-5, -4, and -3. Single dose of CD19/BCMA-Targeted Universal Chimeric Antigen Receptor T Cells (KN3601) will infused using dose-escalation strategy.

Первичные конечные точки

• Incidence of Dose-Limiting Toxicity (DLT) [Срок оценки: up to 24 months after infusion]
• The overall response rate (ORR) [Срок оценки: up to 24 months after infusion]

Критерии участия

Критерии включения

• Aged 18 to 75 years inclusive, either gender;
• Adequate function of major organs as defined below:

• Absolute neutrophil count ≥ 1.0 × 10⁹/L, hemoglobin ≥ 60 g/L, platelet count ≥ 50 × 10⁹/L;
• Hepatic function: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; total bilirubin (TBIL) ≤ 1.5 × ULN;
• Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN;
• Cardiac function: hemodynamically stable, left ventricular ejection fraction (LVEF) ≥ 50%;
• Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must use a medically acceptable contraceptive method or practice abstinence during study treatment and for at least 6 months after the end of treatment.Female subjects of childbearing potential must have a negative serum HCG test within 7 days prior to enrollment and must not be breastfeeding;
• Voluntarily agree to participate in this clinical study, provide written informed consent, demonstrate good compliance, and be willing to comply with follow-up procedures;
• Diagnosis of primary membranous nephropathy confirmed by renal biopsy pathology;
• Meet the clinical criteria for high-risk or relapsed/refractory membranous nephropathy, defined as:

High-risk patients meeting any of the following:

• Estimated glomerular filtration rate (eGFR, CKD-EPI equation) < 60 mL/min/1.73 m², and/or urinary protein > 8 g/day for ≥ 6 months;
• Normal eGFR, urinary protein > 3.5 g/day despite ACEI/ARB treatment for 6 months with < 50% reduction in proteinuria, plus serum albumin < 25 g/L or anti-PLA2R antibody (aPLA2R) > 50 RU/mL; Refractory membranous nephropathy: inadequate response or resistance to prior immunosuppressive therapy (including corticosteroids and/or cytotoxic agents, immunosuppressants and/or biologics), defined as persistent urinary protein ≥ 3.5 g/day with < 50% reduction from baseline; Relapsed membranous nephropathy: recurrence (24-hour urinary protein ≥ 3.5 g) after achieving complete or partial remission (CR/PR) following treatment;
• For relapsed/refractory membranous nephropathy patients during screening: eGFR ≥ 45 mL/min/1.73 m².

Критерии исключения

• Subjects with known allergic reaction, hypersensitivity, intolerance, or contraindication to CD19/BCMA universal CAR-T or any components of the study drugs (including fludarabine, cyclophosphamide, and tocilizumab), or a history of severe allergic reaction in the past.
• Presence or suspicion of uncontrolled or treatable fungal, bacterial, viral, or other infections.
• Central nervous system diseases caused by autoimmune or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis).
• Subjects with severe cardiac diseases, such as angina pectoris, myocardial infarction, heart failure, arrhythmia, etc.
• Subjects with congenital immunoglobulin deficiency.
• Subjects with other malignant tumors (excluding non-melanoma skin cancer and carcinoma in situ of the cervix, bladder, or breast with disease-free survival > 5 years).
• Subjects with end-stage renal failure.
• Subjects positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV DNA titer above the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody and HCV RNA; subjects positive for human immunodeficiency virus (HIV) antibody; subjects with positive syphilis test.
• Subjects with psychiatric disorders and severe cognitive impairment.
• Subjects who participated in other clinical trials within 6 months prior to enrollment.
• Pregnant or lactating females, or females intending to become pregnant during the study.
• Subjects with hypertension or diabetes mellitus that cannot be controlled by medication.
• Subjects for whom the investigator considers there are other reasons for ineligibility.
• Secondary membranous nephropathy (e.g., associated with hepatitis B, systemic lupus erythematosus, drug-related, malignancy-related, etc.), or concurrent renal disease confirmed by renal biopsy.
• Type 1 or type 2 diabetes mellitus.

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

• The First Affiliated Hospital of Zhejiang Chinese Medical University — Ханчжоу

Идентификаторы

NCT: NCT07423572 · 2026-KLS-021-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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