NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy

Study Description: This protocol will test whether NT-I7 is a viable strategy for promoting immune reconstitution in lymphopenic patients with PML. Twelve evaluable adults with PML and lymphopenia (CD4 or CD8 T cell count of \<=200 cells/dL), without a history of autoimmune disease affecting vital organs, will complete this pilot study. Patients will be observed as inpatient for the first 7 days following any experimental drug dosing. To follow, patients will return to NIH for a second 7-day inpatient stay by Day 21, and then for scheduled outpatient visits at NIH at month 2, 3, 6, 9 and 12 following any drug dosing. Follow up phone calls will be conducted at month 4, 5, 7 and 8. Patients may be eligible for a second dose of NT-I7 at higher dose if target ALC (1000/microliter) not reached, or at same dose if initial response is adequate but not sustained, for a maximum of 3 doses. The primary outcome measure is change in absolute lymphocyte counts (ALC). Secondary outcomes include safety and tolerability. Exploratory clinical, radiological, and laboratory measures will be obtained to investigate mechanism of action of NT-I7 and for biomarker development. Objectives: Primary Objective: To determine the kinetics and magnitude of effect of NT-I7 on absolute lymphocyte counts in patients with PML and underlying lymphopenia from various causes, in order to inform appropriate design of a future study. Secondary Objectives: (1) To assess safety and tolerability of NT-I7. (2) To determine kinetics and magnitude of effect of NT-I7 on lymphocyte subsets. (3) To investigate effect of NT-I7 on PML disease course. (4) To investigate mechanism of action of NT-I7. Endpoints: Primary Endpoint: Change in absolute lymphocyte counts (ALC) over 6 months. Secondary Endpoints: (1) Adverse event tables. (2) Change in lymphocyte subset counts, including CD4, CD8 and CD19 positive cells (3) Change in standardized disability rating scales, PML lesion extension by brain MRI, viral quantification in CSF and survival. (4) Exploratory serological and CSF measures to investigate immune response to JCV and mechanism of action of NT-I7.