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

Phase 3Not Yet RecruitingNCT06276504

Assistance Publique - Hôpitaux de Paris33 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Progressive Multifocal Leukoencephalopathy

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation

Paris, France

Hôpital Pitié-Salpêtrière - Service d'hématologie clinique

Paris, France

Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales

Paris, France

Outcomes

Primary Outcomes

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 Outcomes

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

Repeated measures of neurological status

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)

Repeated measures of degree of disability or dependence in the daily activities in neurological conditions

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

Repeated measures of neurological outcome and degree of disability in neurological conditions

Time frame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months

Relapse or progression

Adjudication by a dedicated committee ; based on clinical evolution, JCV PCR in CSF, brain MRI

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

Adjudication by a dedicated committee

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

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

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts