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Not yet recruiting NCT06276504

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

Phase II / Phase III Interventional Progressive Multifocal Leukoencephalopathy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection.
Who it may be relevant to
Registry conditions: Progressive Multifocal Leukoencephalopathy. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Overview

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.

Interventions

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

Primary outcome measures

  • 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 [Time frame: At baseline (Day 0), 1 month, 2 months and 3 months]
Secondary outcome measures (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 [Time frame: 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) [Time frame: 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 [Time frame: At baseline (Day 0), 1 month, 2 months and 3 months]
  • Evolution of National Institutes of Health Stroke Scale (NIHSS) score [Time frame: 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) [Time frame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months]
  • Evolution of Glasgow Outcome Scale Extended (GOS-E) score [Time frame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months]
  • Relapse or progression [Time frame: From baseline to end of participation, a maximum of 12 months]
  • Death (and date of death) [Time frame: From baseline to end of participation, a maximum of 12 months]
  • Cause specific death: death related to PML [Time frame: From baseline to end of participation, a maximum of 12 months]
  • Any adverse event classified by using US NCI CTCAE [Time frame: From baseline to end of participation, a maximum of 12 months]

Eligibility criteria

Inclusion criteria

  • 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)

Exclusion criteria

  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

France · 3 centers
  • 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

Identifiers

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

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗