Clinical trial NCT06276504: Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection
Official title: Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Progressive Multifocal Leukoencephalopathy
Keywords: Progressive Multifocal Leukoencephalopathy
Checkpoint inhibitors
Pembrolizumab
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-02-26
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old
2. Diagnosis of definite PML since less than 2 months according to American Academy of Neurology
3. Presence of JCV in the CSF in the last CSF sampling.
4. Signed informed consent (from the patient, or if unable to consent, from a surrogate)
5. 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:

1. Patients in whom immune reconstitution is achievable (HIV infection - Multiple sclerosis - Auto-immune and inflammatory diseases)
2. Patients who have received solid organ transplantation
3. Hypersensitivity to the active substance or to any of the excipients
4. Life expectancy less than 1 month
5. Pregnancy or lactating women or planning birth during the study period
6. Having previously been treated by anti-PD1mAb
7. Patient receiving IL-2 or IL-7 for the treatment of PML at inclusion
8. Patient whose weight is \> 100kg
9. 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)\]
10. Patient without national health insurance, and patient on AME (state medical aid)
11. Patient under guardianship or curatorship
12. Patient deprived of their liberty by a judicial or administrative decision

Primary outcomes:
measure: 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
timeFrame: At baseline (Day 0), 1 month, 2 months and 3 months
Secondary outcomes:
measure: 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
timeFrame: At baseline (Day 0), 1 month, 2 months and 3 months
measure: Evolution of the JCV viral load in the CSF (repeated measures JCV PCR in CSF)
timeFrame: At baseline (Day 0), 1 month, 2 months and 3 months
measure: Repositivation of JCV PCR: at least a positive result following at least a negative result
timeFrame: At baseline (Day 0), 1 month, 2 months and 3 months
measure: Evolution of National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Evolution of 6-item Modified Rankin Scale score (includes death as most severe state)
timeFrame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Evolution of Glasgow Outcome Scale Extended (GOS-E) score
timeFrame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Relapse or progression
timeFrame: From baseline to end of participation, a maximum of 12 months
measure: Death (and date of death)
timeFrame: From baseline to end of participation, a maximum of 12 months
measure: Cause specific death: death related to PML
timeFrame: From baseline to end of participation, a maximum of 12 months
measure: Any adverse event classified by using US NCI CTCAE
timeFrame: From baseline to end of participation, a maximum of 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière - Service d'hématologie clinique
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales
Study officials:
References: