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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-cells

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.
    • Que

      Detailed Summary:

      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 2x10^6 PyVST/kg (+/-10%) up to 2 times to each subject if needed.

      Outcome Measures

      Same as current

      Current Secondary Outcome:

      • JCV DNA titer in cerebrospinal fluid [ Time Frame: 28 days p tx ]
      • Clinical outcomes [ Time Frame: 28 days p tx ]
      • Survival [ Time Frame: 1 yr p tx ]
      • MRI outcomes [ Time Frame: 28 days p tx ]


      Original Secondary Outcome:

      • JCV DNA titer in cerebrospinal fluid [ Time Frame: 28 days p tx ]
      • Clinical outcomes [ Time Frame: 28 days p tx ]
      • Survival [ Time Frame: 1 yr p tx ]


      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: February 27, 2016
      Date Started: February 19, 2016
      Date Completion: February 15, 2018
      Last Updated: May 12, 2017
      Last Verified: February 13, 2017