Clinical trial NCT06990087: T-cell Therapy in Patients With PML
Official title: CurePML - Allogeneic HPyV-2-specific T-cell Therapy in Patients With Progressive Multifocal Leukoencephalopathy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Progressive Multifocal Leucoencephalopathy (PML)
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2025-05-25
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.

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.

Eligibility 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)

Primary outcomes:
measure: Demonstrate efficacy of treatment
timeFrame: 6 months after diagnosis
Secondary outcomes:
measure: Safety assessment
timeFrame: During 12 months from baseline
measure: Safety assessment
timeFrame: At 12 months from baseline
measure: Assessment of potential inflammatory safety concerns
timeFrame: During 6 months from baseline
measure: Assessment of potential inflammatory safety concerns
timeFrame: During 6 months from baseline
measure: Assessment of potential inflammatory safety concerns
timeFrame: During 6 months from baseline
measure: Safety assessment of potential electrolyte imbalance
timeFrame: During 6 months from baseline
measure: Safety assessment of potential renal dysfunction
timeFrame: During 6 months from baseline
measure: Safety assessment of potential renal dysfunction
timeFrame: During 6 months from baseline
measure: Safety assessment of potential liver dysfunction
timeFrame: During 6 months from baseline
measure: Safety assessment of potential liver dysfunction
timeFrame: During 6 months from baseline
measure: Safety assessment of potential coagulation disorder
timeFrame: During 6 months from baseline
measure: Safety assessment of potential coagulation disorder
timeFrame: During 6 months from baseline
measure: Rate of development of IRIS
timeFrame: During 6 months from baseline
measure: Assessment of neurological status by Modified Rankin Scale (mRS)
timeFrame: Change from baseline after 6 months
measure: Assessment of neurological status by Karnofsky Performance Status Index
timeFrame: Change from baseline after 6 months
measure: Assessment of neurological status by Montreal Cognitive Assessment (MoCA)
timeFrame: Change from baseline after 6 months
measure: Determine change in viral load
timeFrame: Change from baseline after 6 months
measure: Evaluation of quality of life improvements by quality of life questionnaire (EQ-5D-5L)
timeFrame: Change from baseline after 6 months
measure: Analysis of immunological response
timeFrame: Change from baseline after 6 months
measure: Determine lesion volume
timeFrame: Change from baseline after 6 months
measure: Evaluation of survival
timeFrame: At month 12
Other outcomes:
Locations:
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