T-cell therapy for progressive multifocal leukoencephalopathy (PML).
CurePML - Allogeneic HPyV-2-specific T-cell Therapy in Patients With Progressive Multifocal Leukoencephalopathy
This trial will test whether human allogeneic HPyV-2-specific T cells are safe and can improve neurological function, quality of life, and survival in adults with recent PML.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 23 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Hannover Medical School Academic / other |
| Drugs / interventions | natalizumab, CAR T, chemotherapy |
| Locations | 6 sites (München, Bavaria and 5 other locations) |
| Trial ID | NCT06990087 on ClinicalTrials.gov |
What this trial studies
This phase 2 interventional trial will give adults with recent HPyV-2–positive PML up to three doses of human allogeneic HPyV-2-specific T-lymphocytes (one fresh dose at baseline and two cryopreserved doses at weeks 2 and 6). The donor-derived T-cell apheresis concentrates are targeted to HPyV-2 and are administered to see if they are safe and produce neurologic, quality-of-life, or survival benefits beyond current care. Eligible patients are adults (≥18) with PML diagnosed within 60 days and HPyV-2 detected in CSF or brain biopsy, while several causes of PML (including HIV- and natalizumab-associated cases) and other serious comorbidities are excluded. This is the first controlled trial using this specific T-cell approach and aims to generate standardized safety and early efficacy data beyond small compassionate-use reports under ICH-GCP.
Who should consider this trial
Good fit: Adults (≥18) with recent (≤60 days) HPyV-2–positive PML who meet the inclusion criteria and do not have excluded causes (e.g., HIV or natalizumab-associated PML) are the ideal candidates.
Not a fit: Patients with HIV-associated PML, natalizumab-associated PML, PML shortly after stem-cell transplant or CAR-T therapy, chronic lymphocytic leukemia–related PML, ongoing chemotherapy, or severe concurrent infections are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this therapy could help clear HPyV-2 from the brain, improve neurological function and quality of life, and increase survival for people with PML.
How similar studies have performed: Only small case series and compassionate-use reports have suggested possible benefit from HPyV-2–specific T cells, so this controlled trial represents a novel and needed step.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Adults\* aged ≥ 18 years with PML (diagnosed ≤ 60 days before screening) associated with one or more of the following risk factors: lymphoproliferative diseases, immunosuppressive therapy, or lymphopenia * Signed written informed consent from subject and/or legal representative * HPyV-2 detection in CSF by PCR analysis or in brain biopsy Exclusion Criteria: * PML caused by HIV * PML caused by natalizumab * PML occurring within five 5 years after hematopoietic stem-cell transplantation or CAR T cell therapy, or resulting from chronic lymphocytic leukemia (CLL) * Patients who are unable to follow the study protocol, either on their own or with the support of a reliable representative, will be excluded * Pregnancy or breastfeeding * Currently receiving chemotherapy * Present (within 2 weeks before screening visit) and continuous treatment with immune checkpoint inhibition therapy * Severe infections other than PML (e.g. sepsis, pneumonia) * Hypersensitivity to any of the components of the medications used * Inability to undergo MRI examination (e.g. implanted incompatible medical devices, claustrophobia) * Participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
Where this trial is running
München, Bavaria and 5 other locations
- LMU Klinikum Campus Großhadern — München, Bavaria, Germany (Not_yet_recruiting)
- Universitätsklinikum Marburg — Marburg, Hesse, Germany (Not_yet_recruiting)
- Hannover Medical School — Hanover, Lower Saxony, Germany (Recruiting)
- Universitätsklinikum Düsseldorf — Düsseldorf, North Rhine-Westphalia, Germany (Not_yet_recruiting)
- Universitätsklinikum Essen — Essen, North Rhine-Westphalia, Germany (Not_yet_recruiting)
- Universitätsklinikum Schleswig-Holstein — Kiel, Schleswig-Holstein, Germany (Not_yet_recruiting)
Study contacts
- Study coordinator: Thomas Skripuletz, Prof. Dr.
- Email: skripuletz.thomas@mh-hannover.de
- Phone: +49 511 532
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.