Progressive Multifocal Leukoencephalopathy
Conditions
Keywords
Progressive Multifocal Leukoencephalopathy, Checkpoint inhibitors, Pembrolizumab
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.
Interventions
DRUGPembrolizumab, 25 mg/ml solution for intravenous (IV) injection
Pembrolizumab administration at D0, M1 and M2
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | At baseline (Day 0), 1 month, 2 months and 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evolution of the JCV viral load in the CSF (repeated measures JCV PCR in CSF) | 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 | At baseline (Day 0), 1 month, 2 months and 3 months | — |
| Evolution of National Institutes of Health Stroke Scale (NIHSS) score | At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months | Repeated measures of neurological status |
| Evolution of 6-item Modified Rankin Scale score (includes death as most severe state) | At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months | Repeated measures of degree of disability or dependence in the daily activities in neurological conditions |
| 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 | At baseline (Day 0), 1 month, 2 months and 3 months | — |
| Relapse or progression | From baseline to end of participation, a maximum of 12 months | Adjudication by a dedicated committee ; based on clinical evolution, JCV PCR in CSF, brain MRI |
| Death (and date of death) | From baseline to end of participation, a maximum of 12 months | — |
| Cause specific death: death related to PML | From baseline to end of participation, a maximum of 12 months | Adjudication by a dedicated committee |
| Any adverse event classified by using US NCI CTCAE | From baseline to end of participation, a maximum of 12 months | — |
| Evolution of Glasgow Outcome Scale Extended (GOS-E) score | At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months | Repeated measures of neurological outcome and degree of disability in neurological conditions |
Countries
France
Contacts
Primary ContactValérie POURCHER, Pr
Backup ContactTUBACH Florence, Pr
Outcome results
None listed