protocolSection identificationModule nctId: NCT06276504, orgStudyIdInfo id: APHP211001, secondaryIdInfos id: 2023-503520-31-00, type: OTHER, domain: EU CT number, briefTitle: Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection, acronym: PENALTY, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04, primaryCompletionDateStruct date: 2028-04, completionDateStruct date: 2028-04, studyFirstPostDateStruct date: 2024-02-26, lastUpdatePostDateStruct date: 2024-02-26, sponsorCollaboratorsModule leadSponsor name: Assistance Publique - Hôpitaux de Paris, class: OTHER, descriptionModule briefSummary: 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., conditionsModule conditions: Progressive Multifocal Leukoencephalopathy, designModule studyType: INTERVENTIONAL, phases: PHASE2, phases: PHASE3, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 33, type: ESTIMATED, armsInterventionsModule interventions name: Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection, outcomesModule primaryOutcomes measure: 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, secondaryOutcomes measure: 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, secondaryOutcomes measure: Evolution of the JCV viral load in the CSF (repeated measures JCV PCR in CSF), secondaryOutcomes measure: Repositivation of JCV PCR: at least a positive result following at least a negative result, secondaryOutcomes measure: Evolution of National Institutes of Health Stroke Scale (NIHSS) score, secondaryOutcomes measure: Evolution of 6-item Modified Rankin Scale score (includes death as most severe state), secondaryOutcomes measure: Evolution of Glasgow Outcome Scale Extended (GOS-E) score, secondaryOutcomes measure: Relapse or progression, secondaryOutcomes measure: Death (and date of death), secondaryOutcomes measure: Cause specific death: death related to PML, secondaryOutcomes measure: Any adverse event classified by using US NCI CTCAE, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation, city: Paris, zip: 75013, country: France, contacts name: Nicolas WEISS, Pr, role: CONTACT, phone: +33 (0)1 42 16 27 70, email: nicolas.weiss@aphp.fr, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Hôpital Pitié-Salpêtrière - Service d'hématologie clinique, city: Paris, zip: 75013, country: France, contacts name: Damien ROOS-WEIL, Dr, role: CONTACT, phone: +33 (0)1 42 16 15 96, email: damien.roosweil@aphp.fr, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales, city: Paris, zip: 75013, country: France, contacts name: Valérie POURCHER, Pr, role: CONTACT, phone: +33 (0)1 42 16 02 62, email: valerie.martinez@aphp.fr, geoPoint lat: 48.85341, lon: 2.3488, hasResults: False