Anti-CD19 CAR-T Cell Therapy for Patients With Refractory Systemic Lupus Erythematosus

Обзор

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell dysfunction leading to the production of autoantibodies that play a key role in the onset and progression of the disease. In the treatment of SLE today, glucocorticosteroid hormones, cytostatics (azathioprine, cyclophosphamide, mycophenolate mofetil, hydroxychloroquine, etc.), and biological therapy (rituximab, belimumab) are widely used. However, this therapy has limitations: firstly, it does not always control the autoimmune process and, secondly, it has side effects. Recent global data on the use of CAR T cells in patients with SLE show promising results, including rapid and durable remission, without the need for disease-modifying drugs and glucocorticoids. The use of the so-called academic CAR-T cell products can improve availability and affordability of this therapy option. The aim of this clinical study is to evaluate the efficacy and safety of academic CAR-T cells in refractory SLE patients.

Вмешательства

• Биопрепарат CAR T cells chimeric antigen receptor cells
  academical CAR-T product was manufactured using lentiviral vector encoding anti-CD19 CAR.

Первичные конечные точки

• SELENA-SLEDAI activity index assessment and serologic remission (defined as normal level of primary (dsDNA and/or antiSm) and antiphospholipid antibodies (lupus anticoagulant (LA), AT to cardiolipinanti-dsDNA and normal complement C3 and C4 levels) [Срок оценки: 36 months after CAR-T cells infusion]

Вторичные конечные точки (1)

• Evaluation of CAR T-Cell-Related Toxicities [Срок оценки: Start from 0 day up to 30 days after CAR-T cells infusion]

Критерии участия

Критерии включения

• A confirmed diagnosis of SLE according to the 2019 EULAR/ACR criteria.
• Subacute or acute SLE.
• SLE activity according to the SELENA-SLEDAI disease activity index screening score ≥6 and/or the requirement for prednisolone (or equivalent doses of methylprednisolone) at a dose greater than 7.5 mg/day (6 mg/day for methylprednisolone) to maintain lower disease activity.
• A history of two or more prior therapies (one of the drugs mycophenolate mofetil or cyclophosphamide, or the development of side effects/intolerance to these drugs).
• Patients aged 18 years or older.
• A medical consultation on the need for this treatment method using cell therapy.
• Written informed consent from the patient for treatment.
• Patient compliance with the treatment protocol.
• Adequate organ function.

Критерии исключения

• Any change in therapy within 90 days prior to the planned administration of CAR-T cell therapy.
• Patient requiring renal replacement therapy.
• Active hepatitis B or active hepatitis C (HCV RNA positive).
• HIV-infected patients.
• Uncontrolled acute life-threatening bacterial, viral, or fungal infection (e.g., positive blood culture ≤ 72 hours before infusion).
• Unstable angina and/or myocardial infarction within 6 months prior to screening.
• Previous or concomitant malignancy with the exception of:

• basal cell or squamous cell carcinoma (adequate wound healing is required before study entry);
• In situ carcinoma of the cervix or breast, without evidence of recurrence for at least 3 years prior to study entry;
• A primary malignant tumor that has been completely resected and in complete remission for ≥ 5 years.
• Pregnant and lactating women.
• Intolerance to the excipients of the cell product.
• Cardiac arrhythmia not controlled by medical therapy.
• Patients with active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis).
• The presence of any primary immunodeficiency.
• Socioeconomic or geographic circumstances that cannot guarantee adequate compliance with the protocol requirements for treatment and follow-up.

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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Беларусь · 1 центр

• NN Alexandrov National Cancer Centre of Belarus — Lyasny

Идентификаторы

NCT: NCT07720310 · 20251677

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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