UCAR T-cell Therapy Targeting CD19/BCMA in Patients With r/r Systemic Lupus Erythematosus

Официальное название

A Clinical Study Evaluating the Safety and Preliminary Efficacy of Universal Allogeneic CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapsed / Refractory Systemic Lupus Erythematosus

Обзор

This is an open label, single-site, dose-escalation study in up to 18 participants with relapsed or refractory Systemic lupus erythematosus. This study aims to evaluate the safety and efficacy of the treatment with universal CD19/BCMA CAR T-cells.

Подробное описание

This is an investigator-initiated trial to evaluate the safety and efficacy of universal CD19/BCMA CAR T-cells in Relapsed or Refractory Systemic lupus erythematosus.

Study intervention consists of a single infusion of universal CAR T-cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

Interim analysis will be performed when participants finish the visit 90 days after CAR T-cell infusion.

Вмешательства

• Биопрепарат UCAR T-cell group
  A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells

Первичные конечные точки

• The number and severity of dose-limiting toxicity (DLT) events [Срок оценки: Within 28 Days After UCAR T-cell Infusion]
• The total number, incidence, and severity of AEs [Срок оценки: Up to 90 days After UCAR T-cell Infusion]
• Clinical response [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Meet the 2019 European League against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus; The diagnosis of lupus nephritis was consistent with renal biopsy within 6 months prior to the study, and the histological diagnosis (ISN/RPS2018 LN classification) was active nephritis type III or IV with or without type V. Meet the definition of refractory recurrence: conventional treatment remains ineffective for more than 6 months, or disease activity reappears after remission. Conventional treatment is defined as the use of glucocorticoids, along with one or more of the following immunomodulatory drugs: cyclophosphamide, antimalarial drugs, azathioprine, Mycophenolate Mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab, Beliumab, and Telitacicept.
• SLEDAI-2000 ≥8；
• The NIH activity index (AI) of lupus nephritis was >2, and the chronicity index (CI) was increased; Urinary protein: creatinine ratio (UPCR)>1.0g/g, or 24-hour urinary protein >0.5g, with or without active urinary sediment with red blood cell precipitation.
• Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
• Functional requirements for major organs are as follows:

• The bone marrow function needs to meet: a Neutrophil count ≥ 0.5× 10 \^ 9/L; b. Hemoglobin ≥60g/L: c. Platelets ≥ 20 × 10 \^ 9/L.
• Liver function: ALT ≤ 3 × UL; AST ≤ 3×ULN# Total bilirubin ≤ 2.0 ×ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN).
• Renal function: creatinine clearance rate (CrCl) ≥ 30 ml/min(Cockcroft/Gault formula, excluding acute CrCl decline caused by the disease itself).
• ECOG：0-1；
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
• Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Критерии исключения

• Subjects with a history of severe drug allergies or allergic tendencies.
• Presence or suspicion of uncontrolled or treatment-required fungal,bacterial, viral, or other infections.
• Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis).
• Subjects with insufficient cardiac function
• Subjects with congenital immunoglobulin deficiencies
• History of malignancy within five years
• Subjects with end-stage renal failure
• Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer higher than the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV)
• Subjects with psychiatric disorders and severe cognitive impairments
• Subjects who had participated in other clinical trials within 3 months prior to enrollment
• Subjects who have used immunosuppressive agents or biologics with therapeutic effects on the disease within five half-life before enrollment
• Pregnant women or women planning to conceive
• Subjects that the investigator believes have other reasons that make them unsuitable for inclusion in this study.

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 medical college of zhejiang university — Ханчжоу

Идентификаторы

NCT: NCT06920433 · QH-ZY-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗