Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells

NCT02694783 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 16007216-N-0072
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Progressive Multifocal Leukoencephalopathy

Keywords

HLA Matched; JCV; Donor; PyVST; PML

Outcome Measures

Primary Outcomes (1)

• 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

  ongoing

Secondary Outcomes (4)

• PML lesion volume

  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

• Modified Rankin Score

  Change from baseline to day 28

• JC viral load in CSF

  Change from baseline to day 28

Study Arms (1)

Treatment Arm

EXPERIMENTAL

ex vivo generated polyomavirus-specific T cells from HLA-matched donor

Biological: PyVST

Interventions

PyVST BIOLOGICAL

ex vivo generated polyomavirus-specific T cells from HLA-matched donor

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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
• 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.
• Ability to provide informed consent at the time of enrollment
• First degree relative of patient (sibling, parent/child)

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 34302788 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukoencephalopathy, Progressive Multifocal

Condition Hierarchy (Ancestors)

Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Virus Diseases; Polyomavirus Infections; DNA Virus Infections; Slow Virus Diseases; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Neuroinflammatory Diseases

Study Officials

• Irene CM Cortese, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2016
• First Posted: March 1, 2016
• Study Start: March 28, 2016
• Primary Completion: December 13, 2019
• Study Completion: March 6, 2020
• Last Updated: May 1, 2026

Record last verified: 2026-04-29

Locations

US (1)