Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells
- Conditions
- Progressive Multifocal Leukoencephalopathy
- Interventions
- Registration Number
- NCT02694783
- Brief Summary
Background:
Progressive Multifocal Leukoencephalopathy (PML) is a brain infection in people with a weakened immune system. Researchers think polyoma virus specific T cells (PyVST) therapy can treat PML. The PyVST cells are made from blood cells of a healthy relative. They are grown in a lab to expand the virus-killing cells, then given to the person with PML.
Objective:
To test whether PyVST safely treats PML.
Eligibility:
* Adults ages 18 and older with PML
* Healthy adults ages 18 and older who have:
* Been screened under protocol 97-H-0041
* A sibling, parent, or child with PML and matching cells
Design:
* Participants will be screened with:
* Medical history
* Physical exam
* Blood and urine tests
* PML participants will also be screened with:
* Cerebrospinal fluid removed by needle in the back.
* MRI: A dye is injected in a vein. They lie on a table that slides into a cylinder.
* Questionnaires
Healthy participants will have apheresis: Blood flows through a needle in one arm into machine that separates blood cells needed for donation. The rest of the blood is returned by needle to the other arm. Some participants may have a central line placed in a vein instead. They can have apheresis up to 3 times, at least 28 days apart.
Participants with PML will receive the PyVST cells by needle in the arm. They will stay in the hospital 1 week. They can do this up to 3 times, at least 28 days apart. After each infusion, they will have weekly visits for 1 month. Then they will have 4 visits over 1 year. Visits include repeats of screening tests.
- Detailed Description
Objective
This pilot clinical trial will aim to determine the feasibility and potential toxicities associated with treating patients with progressive multifocal leukoencephalopathy (PML) with polyomavirus (PyV)-specific partially matched polyclonal allogeneic T cells. It will further provide initial efficacy data for this indication.
Study Population
Up to 18 subjects with definite PML, defined as clinical signs and MRI compatible with active PML and the presence of JCV by PCR in CSF. Subjects must be 18 years of age or older and must have a first degree, partially HLA- matched relative able and willing to act as a donor of lymphocytes. Subjects with underlying reversible immunosuppression (i.e.- HIV or MS status post treatment with natalizumab), or subjects with uncontrolled malignancy will be excluded. Subjects with evidence of active CNS inflammation as determined by presence of significant contrast enhancement within the PML lesions by MRI will also be excluded because it is assumed such patients are already mounting an adequate immune response against the infection.
Design
This will be a first-in-human pilot study assessing the feasibility and toxicity profile of NIH PyVST cellular product in subjects with PML. Subjects will be screened under the existing NIH Natural History study of PML (13-N-0017). Sequential enrollment will be spaced at least 28 days apart. An initial fixed dose PyVST infusion (target dose of 1 x 10(6) PyVST/kg (+/- 10%)) will be administered by intravenous (IV) infusion, followed by 2x 10(6) PyVST/kg (+/-10%) up to 2 times to each subject if needed.
Outcome Measures
Safety will be monitored to 28 days continuously with stopping rules based on the treatment-related serious adverse event rate. Secondary outcomes include survival, assessed at day 28 and at 1 year following the last infusion. CSF viral titers, MR imaging, and clinical disability scales will also be collected.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm PyVST ex vivo generated polyomavirus-specific T cells from HLA-matched donor
- Primary Outcome Measures
Name Time Method Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity ongoing Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
- Secondary Outcome Measures
Name Time Method PML lesion volume change from baseline to day 28 Change from baseline to day 28 in PML lesion volume, as seen on brain MRI
Gadolinium enhancement Change in pattern of gadolinium enhancement from baseline to day 3, day 7, day 14, and day 28 Change in pattern of gadolinium enhancement from baseline to day 3, day 7, day 14, and day 28 MRI scans of participants' brains
Modified Rankin Score Change from baseline to day 28 Change from baseline to day 28 in the modified Rankin Score (mRS).
JC viral load in CSF Change from baseline to day 28 Change from baseline to day 28 in JC viral load in CSF
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States