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

Progressive Multifocal Leukoencephalopathy Clinical Trial

— PENALTY  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06276504
• Other study ID #: APHP211001
• Secondary ID: 2023-503520-31-0
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: April 2024
• Est. completion date: April 2028

Study information

• Verified date: February 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Valérie POURCHER, Pr
• Phone: +33 (0)1 42 16 02 62
• Email: valerie.martinez[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 33
• Est. completion date: April 2028
• Est. primary completion date: April 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections
• Leukoencephalopathies
• Leukoencephalopathy, Progressive Multifocal
• Progressive Multifocal Leukoencephalopathy

Intervention

Drug:
• Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection
Pembrolizumab administration at D0, M1 and M2

Locations

Country	Name	City	State
France	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

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Evolution of National Institutes of Health Stroke Scale (NIHSS) score	Repeated measures of neurological status	At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
Secondary	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	At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
Secondary	Evolution of Glasgow Outcome Scale Extended (GOS-E) score	Repeated measures of neurological outcome and degree of disability in neurological conditions	At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
Secondary	Relapse or progression	Adjudication by a dedicated committee ; based on clinical evolution, JCV PCR in CSF, brain MRI	From baseline to end of participation, a maximum of 12 months
Secondary	Death (and date of death)		From baseline to end of participation, a maximum of 12 months
Secondary	Cause specific death: death related to PML	Adjudication by a dedicated committee	From baseline to end of participation, a maximum of 12 months
Secondary	Any adverse event classified by using US NCI CTCAE		From baseline to end of participation, a maximum of 12 months