Progressive Multifocal LeukoencephalopathyPhase 2/3PENALTYNCT06276504
Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection
A Phase 2/3 study testing Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection in people with Progressive Multifocal Leukoencephalopathy, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- What is being tested?
- Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesFrance
- Study dates
- Apr 2024to Apr 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 14Show fewer
- Patient receiving IL-2 or IL-7 for the treatment of PML at inclusion
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites
Hôpital Pitié-Salpêtrière - Médecine Intensive Réanimation
Paris, 75013
Nicolas WEISS, Pr, +33 (0)1 42 16 27 70, nicolas.weiss@aphp.fr
Hôpital Pitié-Salpêtrière - Service d'hématologie clinique
Paris, 75013
Damien ROOS-WEIL, Dr, +33 (0)1 42 16 15 96, damien.roosweil@aphp.fr
Hôpital Pitié-Salpêtrière - Service des Maladies infectieuses et tropicales
Paris, 75013
Valérie POURCHER, Pr, +33 (0)1 42 16 02 62, valerie.martinez@aphp.fr
About this study
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.
- Being tested
- Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection
- Keywords
- Progressive Multifocal Leukoencephalopathy, Checkpoint inhibitors, Pembrolizumab
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab, 25 mg/ml solution for intravenous (IV) injectionDrug
Pembrolizumab administration at D0, M1 and M2
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Pembrolizumab (commercial name: KEYTRUDA; MSD), 25 mg/ml solution for intravenous (IV) injection Receives: Drug: Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From baseline to end of participation, a maximum of 12 months
Death (and date of death)
Measured: From baseline to end of participation, a maximum of 12 months
Cause specific death: death related to PML
Adjudication by a dedicated committee
Measured: From baseline to end of participation, a maximum of 12 months
Any adverse event classified by using US NCI CTCAE
Measured: From baseline to end of participation, a maximum of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study startApr 2024 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06276504
- Sponsor's protocol ID
- APHP211001
- Other IDs
- 2023-503520-31-00, 2023
- Acronym
- PENALTY
- Status last verified
- Feb 2024
- First submitted
- 14 Feb 2024
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection
- ClinicalTrials.gov ID
- NCT06276504
- Acronym / sponsor ID
- PENALTY / APHP211001
- Keywords
- Progressive Multifocal Leukoencephalopathy, Checkpoint inhibitors, Pembrolizumab
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Apr 2024 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 26 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: Pembrolizumab, 25 mg/ml solution for intravenous (IV) injectionPembrolizumab (commercial name: KEYTRUDA; MSD), 25 mg/ml solution for intravenous (IV) injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab, 25 mg/ml solution for intravenous (IV) injectionPembrolizumab administration at D0, M1 and M2 | Drug | Pembrolizumab |
Primary outcome
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
10 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
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)
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
Time frame: At baseline (Day 0), 1 month, 2 months, 3 months, 6 months, and 12 months
Relapse or progression
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2024.
- Individual participant dataSharing planned: Yes. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pembrolizumab, 25 mg/ml solution for intravenous (IV) injection in people with Progressive Multifocal Leukoencephalopathy, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Valérie POURCHER, Pr (+33 (0)1 42 16 02 62, valerie.martinez@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: At baseline (Day 0), 1 month, 2 months and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.