A Phase 2 interventional study of Application of T-lymphocytes in Progressive Multifocal Leucoencephalopathy (PML), sponsored by Hannover Medical School. Recruiting at 7 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-15.
Sponsored by Hannover Medical School · Phase 2, Interventional, and Treatment
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.
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.
29 studies on the registry are indexed under Leukoencephalopathy, Progressive Multifocal; 7 are open to participants now.
This study's planned enrollment of 23 is close to the median of 24 across 15 interventional studies indexed under Leukoencephalopathy, Progressive Multifocal.
Browse Leukoencephalopathy, Progressive Multifocal studies →Hannover Medical School is the lead sponsor of 202 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Study participants receive complete or partially HLA-matched, allogeneic HPyV-2-specific T-lymphocytes
Drug: Application of T-lymphocytes
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
Demonstrate efficacy of treatment
Determine proportion of patients surviving 6 months (overall survival) since diagnosis.
Time frame: 6 months after diagnosis
Safety assessment
Recording of AEs, SAEs, AE of special interest (GvHD, allergic reactions).
Time frame: During 12 months from baseline
Safety assessment
Determine proportion of patients surviving 12 months (via telephone interview).
Time frame: At 12 months from baseline
Assessment of potential inflammatory safety concerns
Laboratory examination of differential blood count (cells/microliter).
Time frame: During 6 months from baseline
Assessment of potential inflammatory safety concerns
Laboratory examination of c-reactive protein (CRP; mg/l).
Time frame: During 6 months from baseline
Assessment of potential inflammatory safety concerns
Laboratory examination of serum-immunoglobulin G (IgG; g/l).
Time frame: During 6 months from baseline
Safety assessment of potential electrolyte imbalance
Laboratory examination of potassium, sodium (mmol/l).
Time frame: During 6 months from baseline
Safety assessment of potential renal dysfunction
Laboratory examination of creatinine (micromol/l).
Time frame: During 6 months from baseline
Safety assessment of potential renal dysfunction
Laboratory examination of urea (mmol/l).
Time frame: During 6 months from baseline
Safety assessment of potential liver dysfunction
Laboratory examination of aspartate aminotransferase (AST; U/l), alanine aminotransferase (ALT; U/l).
Time frame: During 6 months from baseline
Safety assessment of potential liver dysfunction
Laboratory examination of bilirubin (micromol/l).
Time frame: During 6 months from baseline
Safety assessment of potential coagulation disorder
Laboratory examination of coagulation parameters (prothrombin time (INR; ratio).
Time frame: During 6 months from baseline
Safety assessment of potential coagulation disorder
Laboratory examination of partial thromboplastin time (PTT; sec.).
Time frame: During 6 months from baseline
Rate of development of IRIS
Evaluate possible development of immune reconstitution inflammatory syndrome (IRIS) by MRI of the brain and clinical examination.
Time frame: During 6 months from baseline
Assessment of neurological status by Modified Rankin Scale (mRS)
mRS compromising 6 levels of degree of impairment (minimum 0 = no symptoms, maximum 6 = death).
Time frame: Change from baseline after 6 months
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).
Time frame: Change from baseline after 6 months
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).
Time frame: Change from baseline after 6 months
Determine change in viral load
HPyV-2 viral load in CSF quantified by PCR.
Time frame: Change from baseline after 6 months
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%).
Time frame: Change from baseline after 6 months
Analysis of immunological response
HPyV-2specific -T-lymphocyte frequency in blood detected by IFN-gamma cytokine secretion.
Time frame: Change from baseline after 6 months
Determine lesion volume
Determine lesion volume on brain MRI.
Time frame: Change from baseline after 6 months
Evaluation of survival
Evaluation of survival by telephone interview.
Time frame: At month 12
Not enrolling at this site.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Leukoencephalopathy, Progressive Multifocal →