A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan

PRIMARY OBJECTIVES: I. To evaluate the safety and efficacy of a preparative regimen of Yttrium-90 (90\^Y)- labeled anti-cluster of differentiation (CD)20 monoclonal antibody (MAb) (yttrium Y 90 ibritumomab tiuxetan) in combination with fludarabine (fludarabine phosphate) and melphalan followed by allogeneic hematopoietic stem cell transplant (APBSCT) for treatment of patients with B-cell low-grade non-Hodgkin lymphoma (LG NHL), intermediate-grade non-Hodgkin lymphoma (IG NHL) and mantle cell lymphoma (MCL). II. To evaluate the short- and long-term complications of this new preparative regimen, including rates of engraftment, acute and chronic graft-versus-host-disease (GVHD) and infectious complications. III. To estimate the disease response rate, disease relapse (progression) rate, and non-relapse mortality rate. IV. To perform exploratory studies that seek to measure/characterize the expression of costimulatory molecules and impact of these molecules on the natural killer (NK) and T cells of a subset of lymphoma patients pre- post- allogeneic stem cell transplant (ASCT) and the stem cell product from a portion of sibling donors. OUTLINE: REDUCED-INTENSITY CONDITIONING: Patients receive rituximab intravenously (IV) followed by indium In-111 ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. STEM CELL TRANSPLANTATION: Patients undergo APBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3 and continuing for up to 6 months with taper. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 5 years.