Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-HodgkinLymphomas

BACKGROUND: * Epstein-Barr virus (EBV) is a chronic viral infection associated with a heterogeneous group of lymphoproliferative disorders (LPD) and non-Hodgkin lymphomas (NHL). * The shared pathobiology of EBV-positive LPDs and NHLs includes a defect in host mechanisms of immune tolerance and immunosurveillance. * Programmed death-1 (PD-1) is a surface protein present on T cells, B cells, and macrophages that serves a co-inhibitory role to negatively regulate immune responses * PD-1 and its ligands, PD-L1 and PD-L2, are overexpressed in EBV-positive lymphoproliferative disorders and are markers of aggressive behavior. * Blockade of the PD-1 pathway induces T-cell responses against tumor antigens in a variety of cancers, including Hodgkin lymphoma, that lead to clinical remissions. * Nivolumab is a fully human IgG4 monoclonal anti-PD-1 receptor antibody with clinical activity in both indolent and aggressive lymphomas. OBJECTIVE: -To determine the best overall response rate of nivolumab in subjects with EBV-positive LPD and EBV-positive NHL ELIGIBLITY: * Subjects must have a confirmed diagnosis of an EBV-positive LPD, or an EBV-positive NHL confirmed by Laboratory of Pathology, NCI --NOTE: LPD subjects may be previously untreated or relapsed from prior therapy; patients with EBV-positive B-cell NHL subjects must have relapsed from previous treatment with an anthracycline and rituximab-based regimen or be considered not eligible for the same * Adequate bone marrow function (unless disease-related) defined as: * Absolute neutrophil count \>= 750/mcL * Hemoglobin \>= 9g/dL (transfusion permitted) * Platelet count \>= 50,000/mcL (transfusion not permitted) * Age greater than or equal to 12 years \<TAB\> DESIGN: * Phase II study of subjects with EBV-positive LPD and EBV-positive NHL, both relapsed and untreated. * Subjects will be treated with nivolumab 480 mg IV every 4 weeks for up to 2 years if responding disease with clinical improvement and no unacceptable toxicity. * All responding subjects (CR, PR, or SD with clinical benefit) who subsequently relapse or progress within 1 year after discontinuation of study drug are eligible for re-treatment. * An optimal two-stage phase II trial design will be used to rule out a best overall response rate of 20%. If fewer than 3 of the first 17 subjects respond, the study would accrue no more subjects. * Subjects with both EBV-positive LPD and EBV-positive NHL will be enrolled on this protocol for a total of 37 evaluable subjects. In order to allow for inevaluable subjects and screen failures, the accrual ceiling will be set at 40 subjects.