A Study of Lenalidomide and CC-486 With Radiation Therapy in Patients With Plasmacytoma

Inclusion Criteria: Cohort 1: Must meet all the following 3 criteria: * Histologically confirmed newly diagnosed or recurrent solitary plasmacytoma/lytic lesion (recurrent solitary plasmacytomas will be considered based on treating physician discretion for cases where they clinically plan to treat with RT alone) - Minimal marrow involvement (Detectable clonal bone marrow plasma cells by multicolor flow cytometry and \</= 10% clonal plasma cells in a bone marrow biopsy by immunohistochemistry, morphology, or flow cytometry) * Secretory M protein \< 3 g/dL Cohort 2: Must meet all the following criteria: * Relapsed multiple myeloma with plasmacytomas/lytic lesion appropriate for RT on imaging * Relapsed (reappearance of M-spike/serum FLC) or progressive myeloma defined by a 25% increase from nadir in M-spike or involved serum FLB on 2 separate measurements; or with bone marrow involvement by clonal plasma cells detectable by IHC or flow cytometry. * Any prior number of therapies is permitted, including prior radiation therapy * Allogeneic transplant patients are permitted All Cohorts: * Age \>/= 18 years * Surgical resection of plasmacytoma or stabilization surgery is permitted if necessary based on physician judgement * ECOG performance status of 0-1 * Anticipated lifespan greater than 3 months * Able and willing to give valid written informed consent * Creatinine clearance \>/=30ml/min by Cockroft-Gault method. See section below, "Dosing Regimen", regarding lenalidomide …