T-cell Therapy in Patients With PML

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

• Demonstrate efficacy of treatment [Time frame: 6 months after diagnosis]

Secondary outcome measures (12)

• Safety assessment [Time frame: During 12 months from baseline]
• Safety assessment [Time frame: At 12 months from baseline]
• Assessment of potential inflammatory safety concerns [Time frame: During 6 months from baseline]
• Assessment of potential inflammatory safety concerns [Time frame: During 6 months from baseline]
• Assessment of potential inflammatory safety concerns [Time frame: During 6 months from baseline]
• Safety assessment of potential electrolyte imbalance [Time frame: During 6 months from baseline]
• Safety assessment of potential renal dysfunction [Time frame: During 6 months from baseline]
• Safety assessment of potential renal dysfunction [Time frame: During 6 months from baseline]
• Safety assessment of potential liver dysfunction [Time frame: During 6 months from baseline]
• Safety assessment of potential liver dysfunction [Time frame: During 6 months from baseline]
• Safety assessment of potential coagulation disorder [Time frame: During 6 months from baseline]
• Safety assessment of potential coagulation disorder [Time frame: During 6 months from baseline]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 6 centers

• LMU Klinikum Campus Großhadern — München
• Universitätsklinikum Marburg — Marburg
• Hannover Medical School — Hanover
• Universitätsklinikum Düsseldorf — Düsseldorf
• Universitätsklinikum Essen — Essen
• Universitätsklinikum Schleswig-Holstein — Kiel

Identifiers

NCT: NCT06990087 · CurePML · 01EN2302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗