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Progressive Multifocal Leucoencephalopathy (PML)Phase 2NCT06990087

T-cell Therapy in Patients With PML

A Phase 2 study testing Application of T-lymphocytes in people with Progressive Multifocal Leucoencephalopathy (PML), run by Hannover Medical School at 7 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

There is no approved standard treatment für progressive multifocal leukoencephalopathy (PML). The sponsor of the study is developing a new treatment. For this reason, the investigational medicinal product (IMP) called 'human allogenic HPyV-2-specific T cells' is to be tested in this study. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Application of T-lymphocytes
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
7 sitesGermany
Study dates
6 Feb 2026to Nov 2027
Phase
Phase 2
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

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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)

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Thomas Skripuletz, Prof. Dr. contact

+49 511 532 ext. 3120

skripuletz.thomas@mh-hannover.de

7 sites in 1 country

Germany7 sites, 6 recruiting

  • Universitätsklinikum Bonn

    Bonn, North Rhine-Westphalia, 53127

    Not yet recruiting

  • Universitätsklinikum Düsseldorf

    Düsseldorf, North Rhine-Westphalia, 40225

    Withdrawn

  • Universitätsklinikum Essen

    Essen, North Rhine-Westphalia, 45147

    Not yet recruiting

  • Hannover Medical School

    Hanover, Lower Saxony, 30625

    Thomas Skripuletz, Prof. Dr.

    Recruiting

  • Universitätsklinikum Schleswig-Holstein

    Kiel, Schleswig-Holstein, 24105

    Not yet recruiting

  • Universitätsklinikum Marburg

    Marburg, Hesse

    Recruiting

  • LMU Klinikum Campus Großhadern

    München, Bavaria, 81377

    Franziska Hopfner, Prof. Dr.

    Recruiting

Other trials in Germany

About this study

Official title: CurePML - Allogeneic HPyV-2-specific T-cell Therapy in Patients With Progressive Multifocal Leukoencephalopathy

There is no approved standard treatment für progressive multifocal leukoencephalopathy (PML). The sponsor of the study is developing a new treatment. For this reason, the investigational medicinal product (IMP) called 'human allogenic HPyV-2-specific T cells' is to be tested in this study. The sponsor wants to find out whether the IMP is safe, influences the neurological status and improves the quality of the life of patients . It is to be investigated whether the IMP can be used to treat the disease and whether it could have an advantage over the standard therapy in terms of survival rate.

Read the detailed description

Progressive multifocal leukoencephalopathy (PML) is a severe infection of the central nervous system (CNS) caused by reactivation of human polyoma virus 2 (HPyV-2). HPyV-2 usually produces asymptomatic, lifelong persistent or latent infection in the general population. However, in patients with long lasting and profound impairment of cellular immunity, HPyV-2 can reactivate from latency leading to lytic infection of CNS glial cells and thus to encephalitis PML. PML is usually fatal or at least associated with severe disability which makes it a relevant target for the search of appropriate therapeutic options.

The investigational medicinal products (IMPs) under test are fresh and cryopreserved allogeneic HPyV-2-specific T-lymphocyte apheresis concentrates.

Each patient will receive one HPyV-2-specific T-lymphocyte fresh product and two additional cryopreserved products from the same manufacture with the same dose 2 and 6 weeks after baseline, respectively.

This is the first controlled clinical trial to treat patients suffering from PML with this specific methodology of T-cell therapy. The currently available evidence of safety and efficacy is only based on a small series of individual cases treated on a compassionate use basis. This study aims to generate data on safety and first evidence of efficacy within a standardized clinical trial protocol complying to ICH-GCP principles.

Being tested
Application of T-lymphocytes
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.

  • Application of T-lymphocytesDrug

    Dosage form: Infusion; Route of administration: Intravenous; Cell dose: 1-2 x 10.000 viable CD3+ T-lymphocytes per kg bodyweight; Application at three timepoints: baseline, after two weeks, after 6 weeks

Study groups in NCT06990087
Study groupRoleWhat they receive
InterventionExperimentalStudy participants receive complete or partially HLA-matched, allogeneic HPyV-2-specific T-lymphocytes
Receives: Drug: Application of T-lymphocytes

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Demonstrate efficacy of treatment

    Determine proportion of patients surviving 6 months (overall survival) since diagnosis.

    Measured: 6 months after diagnosis

Secondary outcomes (21)

  1. Safety assessment

    Recording of AEs, SAEs, AE of special interest (GvHD, allergic reactions).

    Measured: During 12 months from baseline

  2. Safety assessment

    Determine proportion of patients surviving 12 months (via telephone interview).

    Measured: At 12 months from baseline

  3. Assessment of potential inflammatory safety concerns

    Laboratory examination of differential blood count (cells/microliter).

    Measured: During 6 months from baseline

  4. Assessment of potential inflammatory safety concerns

    Laboratory examination of c-reactive protein (CRP; mg/l).

    Measured: During 6 months from baseline

  5. Assessment of potential inflammatory safety concerns

    Laboratory examination of serum-immunoglobulin G (IgG; g/l).

    Measured: During 6 months from baseline

  6. Safety assessment of potential electrolyte imbalance

    Laboratory examination of potassium, sodium (mmol/l).

    Measured: During 6 months from baseline

  7. Safety assessment of potential renal dysfunction

    Laboratory examination of creatinine (micromol/l).

    Measured: During 6 months from baseline

  8. Safety assessment of potential renal dysfunction

    Laboratory examination of urea (mmol/l).

    Measured: During 6 months from baseline

  9. Safety assessment of potential liver dysfunction

    Laboratory examination of aspartate aminotransferase (AST; U/l), alanine aminotransferase (ALT; U/l).

    Measured: During 6 months from baseline

  10. Safety assessment of potential liver dysfunction

    Laboratory examination of bilirubin (micromol/l).

    Measured: During 6 months from baseline

  11. Safety assessment of potential coagulation disorder

    Laboratory examination of coagulation parameters (prothrombin time (INR; ratio).

    Measured: During 6 months from baseline

  12. Safety assessment of potential coagulation disorder

    Laboratory examination of partial thromboplastin time (PTT; sec.).

    Measured: During 6 months from baseline

  13. Rate of development of IRIS

    Evaluate possible development of immune reconstitution inflammatory syndrome (IRIS) by MRI of the brain and clinical examination.

    Measured: During 6 months from baseline

  14. Assessment of neurological status by Modified Rankin Scale (mRS)

    mRS compromising 6 levels of degree of impairment (minimum 0 = no symptoms, maximum 6 = death).

    Measured: Change from baseline after 6 months

  15. Assessment of neurological status by Karnofsky Performance Status Index

    Karnofsky Performance Status Index compromising 11 levels of functional impairment (minimum 100% = no symptoms, maximum 0% = death).

    Measured: Change from baseline after 6 months

  16. Assessment of neurological status by Montreal Cognitive Assessment (MoCA)

    Montreal Cognitive Assessment (MoCA) compromising 8 categories to detect cognitive impairment (minimum 0 points, maximum 30).

    Measured: Change from baseline after 6 months

  17. Determine change in viral load

    HPyV-2 viral load in CSF quantified by PCR.

    Measured: Change from baseline after 6 months

  18. Evaluation of quality of life improvements by quality of life questionnaire (EQ-5D-5L)

    Quality of life questionnaire (EQ-5D-5L) compromising 5 categories to determine quality of life (minimum 0%, maximum 100%).

    Measured: Change from baseline after 6 months

  19. Analysis of immunological response

    HPyV-2specific -T-lymphocyte frequency in blood detected by IFN-gamma cytokine secretion.

    Measured: Change from baseline after 6 months

  20. Determine lesion volume

    Determine lesion volume on brain MRI.

    Measured: Change from baseline after 6 months

  21. Evaluation of survival

    Evaluation of survival by telephone interview.

    Measured: At month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2025
  2. Study start6 Feb 2026
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06990087
Sponsor's protocol ID
CurePML
Other IDs
01EN2302
Status last verified
Feb 2026
First submitted
29 Apr 2025
Last updated
15 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Application of T-lymphocytes in people with Progressive Multifocal Leucoencephalopathy (PML), run by Hannover Medical School at 7 sites in Germany.

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 3 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. 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 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.

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 Thomas Skripuletz, Prof. Dr. (+49 511 532 ext. 3120, skripuletz.thomas@mh-hannover.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Demonstrate efficacy of treatment (time frame: 6 months after diagnosis). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06990087.

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 15 Oct 2026.

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