Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

PRIMARY OBJECTIVES: I. To estimate the maximum-tolerated dose (MTD) of 90Y-BC8-DOTA (yttrium Y 90 anti-CD45 monoclonal antibody BC8) (anti-cluster of differentiation \[CD\] 45) that can be delivered prior to myeloablative carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and autologous stem cell transplant (ASCT) for patients with high-risk B-non-Hodgkin lymphoma (NHL), T-NHL, and Hodgkin lymphoma (HL). II. To evaluate the efficacy of 90Y-BC8-DOTA when administered at the estimated MTD prior to BEAM chemotherapy and ASCT for patients with high-risk B-NHL, T-NHL, and HL compared to historical controls treated with BEAM alone. SECONDARY OBJECTIVES: I. To describe the toxicity observed from the addition of 90Y-BC8-DOTA to BEAM. II. To optimize the protein dose (Ab) to deliver a favorable biodistribution in the majority of patients. III. To describe response rates and overall survival of patients with high-risk B-NHL, T-NHL, and HL following administration of 90Y-BC8-DOTA plus BEAM prior to ASCT. IV. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD45 targeting. V. To assess the correlation of lymphoma biomarkers with outcomes. VI. To evaluate the effects of nodal-targeted irradiation by 90Y-BC8-DOTA on immune reconstitution following ASCT. OUTLINE: This is a phase I, dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8 followed by a phase II study. Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours twice daily (BID) on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous peripheral blood stem cell (PBSC) transplant on day 0. After completion of study treatment, patients are followed up at 3, 6, and 12 months and then annually thereafter.