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

Phase 2

Not yet recruiting

• Conditions: Progressive Multifocal Leukoencephalopathy
• Interventions: Drug: Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection

• Registration Number: NCT06276504
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-14
• Study First Submitted QC: 2024-02-21
• Last Update Submitted: 2024-02-21
• Study First Posted: 2024-02-26
• Last Update Posted: 2024-02-26
• Study Start: 2024-04
• Primary Completion: 2028-04
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 33

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Any adverse event classified by using US NCI CTCAE	From baseline to end of participation, a maximum of 12 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	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
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
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

Trial Locations

Locations (3)

Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation; 🇫🇷 Paris, France

Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales; 🇫🇷 Paris, France

Hôpital Pitié-Salpêtrière - Service d'hématologie clinique; 🇫🇷 Paris, France