Progressive Multifocal LeukoencephalopathyEarly Phase 1NCT02694783
Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells
A Early Phase 1 study testing PyVST in people with Progressive Multifocal Leukoencephalopathy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- What is being tested?
- PyVST
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2016to 6 Mar 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- Clinically definite PML, defined as clinical signs and MRI compatible with active PML and the presence of JCV by PCR in CSF
- Modified Rankin Scale 1-4, inclusive
- Age 18 or older
- Patient medically stable and able to tolerate travel to NIH
- Available PyVST
- Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study
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- Willing and able to participate in all aspects of trial design and follow-up
- Able to provide informed consent at the time of study enrollment (not required for reinfusions).
- Ability to provide informed consent at the time of enrollment
- First degree relative of patient (sibling, parent/child)
- Age 18 or older
Who cannot join
- Patients with human immunodeficiency virus (HIV infection)
- Patients who have been treated with natalizumab
- Patients with readily reversible immunosuppressive state
- Patients receiving immunosuppressive or immunomodulatory therapies within 28 days of screening for enrollment that could interfere with PyVST function
- Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
- Patients who have received donor lymphocyte infusion (DLI) within 28 days
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- Uncontrolled relapse of malignancy
- Patients with any other associated CNS disease that might confound outcomes
- Patients with contraindication to MRI (including cardiac pacemakers and some infusion pumps, other metallic implants, metallic foreign objects)
- MRI findings consistent with immune system reconstitution inflammatory syndrome (IRIS) and determined to be mounting an adequate immune response to the infection
- Patients with medical contraindication to LP
- For subjects who have previously received PyVST infusions, any treatment-limiting toxicity (defined in Section 8.3) to previous infusions
- Subjects with a positive pregnancy test or who are nursing.
- Sickling hemoglobinopathies including HbSS and HbSC by history and peripheral blood smear; donors with HbAS are acceptable
- HbsAg, anti-HBc, anti-HCV, anti-HIV, anti-HTLV, and RPR
- Cardiovascular instability, severe anemia, inadequate venous access, severe coagulation disorder or any other medical condition that the Principal Investigator or Apheresis Unit staff considers a contraindication to the apheresis procedure or research blood draw.
- Positive pregnancy test
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-cells
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.
Read more
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.
Read the 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.
- Being tested
- PyVST
- Keywords
- HLA Matched, JCV, Donor, PyVST, PML
- 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.
PyVSTBiological
ex vivo generated polyomavirus-specific T cells from HLA-matched donor
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | ex vivo generated polyomavirus-specific T cells from HLA-matched donor Receives: Biological: PyVST |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
Measured: ongoing
Secondary outcomes (4)
PML lesion volume
Change from baseline to day 28 in PML lesion volume, as seen on brain MRI
Measured: change from baseline to day 28
Gadolinium enhancement
Change in pattern of gadolinium enhancement from baseline to day 3, day 7, day 14, and day 28 MRI scans of participants' brains
Measured: Change in pattern of gadolinium enhancement from baseline to day 3, day 7, day 14, and day 28
Modified Rankin Score
Change from baseline to day 28 in the modified Rankin Score (mRS).
Measured: Change from baseline to day 28
JC viral load in CSF
Change from baseline to day 28 in JC viral load in CSF
Measured: Change from baseline to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study start28 Mar 2016
- Primary completion13 Dec 2019
- Study completion6 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irene CM Cortese, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02694783
- Sponsor's protocol ID
- 160072
- Other IDs
- 16-N-0072
- Status last verified
- 29 Apr 2026
- First submitted
- 27 Feb 2016
- Last updated
- 17 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cortese I, Beck ES, Al-Louzi O, Ohayon J, Andrada F, Osuorah I, Dwyer J, Billioux BJ, Dargah-Zada N, Schindler MK, Binder K, Reoma L, Norato G, Enose-Akahata Y, Smith BR, Monaco MC, Major EO, Jacobson S, Stroncek D, Highfill S, Panch S, Reich DS, Barrett J, Nath A, Muranski P. BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study. Lancet Neurol. 2021 Aug;20(8):639-652. doi: 10.1016/S1474-4422(21)00174-5.
PubMed 34302788
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-cells
- ClinicalTrials.gov ID
- NCT02694783
- Acronym / sponsor ID
- 160072
- Keywords
- HLA Matched, JCV, Donor, PyVST, PML
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 28 Mar 2016 (actual)
- Primary completion
- 13 Dec 2019 (actual)
- Study completion
- 6 Mar 2020 (actual)
- First posted
- 1 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Biological: PyVSTex vivo generated polyomavirus-specific T cells from HLA-matched donor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Clinically definite PML, defined as clinical signs and MRI compatible with active PML and the presence of JCV by PCR in CSF
- Modified Rankin Scale 1-4, inclusive
- Age 18 or older
- Patient medically stable and able to tolerate travel to NIH
- Available PyVST
Key exclusion criteria (17 listed)
- Patients with human immunodeficiency virus (HIV infection)
- Patients who have been treated with natalizumab
- Patients with readily reversible immunosuppressive state
- Patients receiving immunosuppressive or immunomodulatory therapies within 28 days of screening for enrollment that could interfere with PyVST function
- Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyVSTex vivo generated polyomavirus-specific T cells from HLA-matched donor | Biological | Treatment Arm |
Primary outcome
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
Time frame: ongoing
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity
4 secondary outcomes
PML lesion volume
Time frame: change from baseline to day 28
Gadolinium enhancement
Time frame: Change in pattern of gadolinium enhancement from baseline to day 3, day 7, day 14, and day 28
Modified Rankin Score
Time frame: Change from baseline to day 28
JC viral load in CSF
Time frame: Change from baseline to day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Derived from this study: PubMed 34302788Cortese I, Beck ES, Al-Louzi O, Ohayon J, Andrada F, Osuorah I, Dwyer J, Billioux BJ, Dargah-Zada N, Schindler MK, Binder K, Reoma L, Norato G, Enose-Akahata Y, Smith BR, Monaco MC, Major EO, Jacobson S, Stroncek D, Highfill S, Panch S, Reich DS, Barrett J, Nath A, Muranski P. BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study. Lancet Neurol. 2021 Aug;20(8):639-652. doi: 10.1016/S1474-4422(21)00174-5.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Irene CM Cortese, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing PyVST in people with Progressive Multifocal Leukoencephalopathy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 11 inclusion and 17 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: finished, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity (time frame: ongoing). 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 NCT02694783, which also lists 1 linked publication.
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 17 Jul 2026; AzTrials last refreshed its copy on 31 Oct 2026.