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

• Register: ClinicalTrials.gov
• Last refreshed on: 30 October 2023
• Main ID: NCT02694783
• Date of registration: 27/02/2016
• Prospective Registration: Yes
• Primary sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Public title: Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells
• Scientific title: A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-cells
• Date of first enrolment: March 28, 2016
• Target sample size: 60
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02694783
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Early Phase 1

Countries of recruitment

United States

Contacts

• Name: Irene CM Cortese, M.D.
• Affiliation: National Institute of Neurological Disorders and Stroke (NINDS)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA - PATIENT:

- 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).

EXCLUSION CRITERIA - PATIENT:

- 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.

INCLUSION CRITERIA - DONOR:

- Ability to provide informed consent at the time of enrollment

- First degree relative of patient (sibling, parent/child)

- Age 18 or older

EXCLUSION CRITERIA - DONOR:

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Progressive Multifocal Leukoencephalopathy

Intervention(s)

Biological: PyVST

Primary Outcome(s)

Characterization of the safety and feasibility of PyVST infusion for the treatment of PML based on development of Treatment Limiting Toxicity [Time Frame: ongoing]

Secondary Outcome(s)

Modified Rankin Score [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]

JC viral load in CSF [Time Frame: Change from baseline to day 28]

PML lesion volume [Time Frame: change from baseline to day 28]

Secondary ID(s)

160072

16-N-0072

Source(s) of Monetary Support

Please refer to primary and secondary sponsors