160072

About this trial

Last updated 2 years ago

Study ID

160072

Status

Completed

Type

Interventional

Phase

Early Phase 1

Placebo

Accepting

18+ Years

All

Not accepting

Healthy Volunteers

Trial Timing

Ended 5 years ago

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.

- 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

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