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

NCT06276504 | Not Yet Recruiting Phase 2

• 2 other identifiers: APHP2110012023-503520-31-00
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

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.

Conditions

Progressive Multifocal Leukoencephalopathy

Keywords

Progressive Multifocal Leukoencephalopathy; Checkpoint inhibitors; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (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

  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)

  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

• 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

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab (commercial name: KEYTRUDA; MSD), 25 mg/ml solution for intravenous (IV) injection

Drug: Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection

Interventions

Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection DRUG

Pembrolizumab administration at D0, M1 and M2

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation

Paris, 75013, France

Location

Hôpital Pitié-Salpêtrière - Service d'hématologie clinique

Paris, 75013, France

Location

Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales

Paris, 75013, France

Location

MeSH Terms

Conditions

Leukoencephalopathy, Progressive Multifocal

Interventions

pembrolizumab; Solutions; Injections

Condition Hierarchy (Ancestors)

Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Virus Diseases; Polyomavirus Infections; DNA Virus Infections; Slow Virus Diseases; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Valérie POURCHER, Pr

CONTACT

+33 (0)1 42 16 02 62; valerie.martinez@aphp.fr

TUBACH Florence, Pr

CONTACT

+33 (0)1 42 16 05 05; urc.pslcfx.psl@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: February 26, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (3)