Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma

PRIMARY OBJECTIVES: I. Identify the maximal tolerated dose (MTD) and safety of lenalidomide up to 10mg following non-myeloablative allogeneic stem cell transplant for multiple myeloma. SECONDARY OBJECTIVES: I. Assess safety and tolerability of weekly bortezomib following non-myeloablative allogeneic stem cell transplant. II. Obtain estimates of non-relapse mortality. III. Obtain estimates of acute and chronic graft-versus-host disease (GVHD). IV. Obtain estimates of 1 year relapse and survival. OUTLINE: This is a dose-escalation study of lenalidomide. PREPARATIVE REGIMEN: Patients receive fludarabine phosphate on days -5 to -3 and undergo total body irradiation (TBI) on day -1. TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant (SCT) on day 0. GVHD PROPHYLAXIS: Patients receive standard GVHD prophylaxis comprising cyclosporine orally (PO) twice daily (BID) beginning on day -1 with taper beginning on day 100, mycophenolate mofetil PO BID on days 1-56, and bortezomib subcutaneously (SC) weekly from day 1 to day 91. MAINTENANCE THERAPY: Beginning on day 100, patients receive lenalidomide PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up monthly for 1 year post-transplant.