Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection

Обзор

This study aims to assess the efficacy and safety of pembrolizumab in immunocompromised patients with progressive multifocal leukoencephalopathy (PML). This phase II, multicenter, single-arm study includes patients with an underlying cause of immunosuppression hardly reversible, i.e. not the patients with HIV nor those receiving biologics for chronic inflammatory diseases. Patients will receive intravenous pembrolizumab (2 mg/kg, maximum 200 mg) at month 0, 1 and 2 (total of three doses). The primary endpoint will be achieving at least one negative result of JCV viral load in cerebrospinal fluid (CSF) within the M0 to M3 period.

Вмешательства

• Препарат Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection
  Pembrolizumab administration at D0, M1 and M2

Первичные конечные точки

• Negativation of JCV viral load in the CSF as assessed by PCR: at least one JCV PCR in the CSF negative in the Day 0 to Month 3 period [Срок оценки: At baseline (Day 0), 1 month, 2 months and 3 months]

Вторичные конечные точки (10)

• Negativation of JCV PCR viral load in the CSF: cumulative incidence of negative JCV viral load measures by PCR in CSF, with death as competing event [Срок оценки: At baseline (Day 0), 1 month, 2 months and 3 months]
• Evolution of the JCV viral load in the CSF (repeated measures JCV PCR in CSF) [Срок оценки: At baseline (Day 0), 1 month, 2 months and 3 months]
• Repositivation of JCV PCR: at least a positive result following at least a negative result [Срок оценки: At baseline (Day 0), 1 month, 2 months and 3 months]
• Evolution of National Institutes of Health Stroke Scale (NIHSS) score [Срок оценки: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months]
• Evolution of 6-item Modified Rankin Scale score (includes death as most severe state) [Срок оценки: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months]
• Evolution of Glasgow Outcome Scale Extended (GOS-E) score [Срок оценки: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months]
• Relapse or progression [Срок оценки: From baseline to end of participation, a maximum of 12 months]
• Death (and date of death) [Срок оценки: From baseline to end of participation, a maximum of 12 months]
• Cause specific death: death related to PML [Срок оценки: From baseline to end of participation, a maximum of 12 months]
• Any adverse event classified by using US NCI CTCAE [Срок оценки: From baseline to end of participation, a maximum of 12 months]

Критерии участия

Критерии включения

• Age ≥ 18 years old
• Diagnosis of definite PML since less than 2 months according to American Academy of Neurology
• Presence of JCV in the CSF in the last CSF sampling.
• Signed informed consent (from the patient, or if unable to consent, from a surrogate)
• For women of childbearing potential: negative serum or urine b-HCG test and agree to use a highly effective contraception methods during 8 months (i.e. until 6 months after end of experimental treatment)

Критерии исключения

• Patients in whom immune reconstitution is achievable (HIV infection - Multiple sclerosis - Auto-immune and inflammatory diseases)
• Patients who have received solid organ transplantation
• Hypersensitivity to the active substance or to any of the excipients
• Life expectancy less than 1 month
• Pregnancy or lactating women or planning birth during the study period
• Having previously been treated by anti-PD1mAb
• Patient receiving IL-2 or IL-7 for the treatment of PML at inclusion
• Patient whose weight is > 100kg
• Participation in other interventional study \[a patient already included in another interventional study for which the treatment can lead to an immunodepression can be included if:

• the investigational treatment has been completed and there is no risk of drug interaction with the administration of Pembrolizumab as defined in PENALTY study
• if this does not alter the study's ability to evaluate the effect of Pembrolizumab in terms of safety and efficacy (from the investigator's point of view)\]
• Patient without national health insurance, and patient on AME (state medical aid)
• Patient under guardianship or curatorship
• Patient deprived of their liberty by a judicial or administrative decision

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

Франция · 3 центра

• Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation — Paris
• Hôpital Pitié-Salpêtrière - Service d'hématologie clinique — Paris
• Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales — Paris

Идентификаторы

NCT: NCT06276504 · APHP211001 · 2023-503520-31-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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