UCAR T-cell Therapy Targeting CD19/BCMA in Patients With r/r Myasthenia Gravis

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 Myasthenia Gravis

Обзор

This is an open label, single-site, dose-escalation study in up to 18 participants with relapsed or refractory Myasthenia gravis. 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 Myasthenia gravis.

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]
• Changes of Myasthenia Gravis Activities if Daily Living (MG-ADL) Score [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• Quantitative Myasthenia Gravis Score (QMG) [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
• Patients with relapsed refractory myasthenia gravis (MG) who have positive abnormal antibodies, the total score of MG-ADL ≥5, and the eye muscle score < 50% of the total score; It is classified as Grade II-IV according to the 2020 MGFA diagnostic criteria.
• Specific requirements include: i. Receiving standardized treatment with at least one immunosuppressant for more than 1 year, and having any of the following malcontrolled conditions: 1) persistent inability to affect daily life; 2) Aggravation of MG symptoms and/or crisis episodes occur despite standard treatment; 3) Inability to tolerate immunosuppressive therapy. ii. plasma exchange or maintenance of intravenous immunoglobulin therapy is required.
• Functional requirements for major organs are as follows:

• The bone marrow function needs to meet: a Neutrophil count ≥ 1.5× 10 \^ 9/L; b. Hemoglobin ≥90g/L: c. Platelets ≥ 80 × 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).
• 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) antibody; individuals positive for syphilis testing.
• 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: NCT06933563 · QH-ZY-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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