Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

PRIMARY OBJECTIVES:

I. To assess the feasibility, safety, and potential efficacy of treating patients with B-Cell non-Hodgkin lymphoma (NHL) with 90Y-ibritumomab tiuxetan, combined with HLA-matched related or unrelated donor hematopoietic cell transplantation.

OUTLINE: Patients receive rituximab intravenously (IV) followed by, no more than 4 hours later, indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -21. Patients undergo gamma camera imaging on day -19. Patients receive rituximab IV followed by, no more than 4 hours later, yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine phosphate IV over 30-60 minutes on days -7 to -5 and undergo low-dose total-body irradiation (TBI) on day 0. After TBI, patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients who undergo PBSCT from a related donor receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). These patients also receive oral mycophenolate mofetil twice daily on days 0 to 27. Patients who undergo PBSCT from an unrelated donor receive oral cyclosporine twice daily on days -3 to 100 followed by a taper over 11 weeks in the absence of GVHD. These patients also receive oral mycophenolate mofetil three times daily on days 0 to 40 followed by a taper to day 96.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then annually thereafter.

Inclusion criteria

• Patients must have a histologically confirmed diagnosis of a lymphoid malignancy expressing the cluster of differentiation (CD)20 antigen and have failed at least one prior standard systemic therapy
• Patients must have evidence of persistent lymphoma by physical examination, radiographic studies, bone marrow evaluation, flow cytometry, or polymerase chain reaction (PCR)
• Creatinine < 2.0
• Bilirubin < 1.5 mg/dL
• Patients must have an expected survival of > 60 days and must be free of major infection including human immunodeficiency virus (HIV)
• Patients must have an HLA-identical related or unrelated donor
• DONOR: Donor eligibility includes both HLA-matched relatives or HLA matched, unrelated volunteer donors; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DRB1 according to FHCRC Standard Practice Guidelines and to the allele level at DQB1; unrelated donors should be identified using matching criteria that follows the FHCRC Standard Practice Guidelines limiting the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1 (Grade1), and accepting up to one allele mismatch as per Standard Practice Grade 2.1 for HLA-A, B, or C
• Donor must consent to granulocyte colony-stimulating factor (G-CSF) (filgrastim) administration and leukapheresis
• Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion criteria

• Systemic anti-lymphoma therapy given in the previous 30 days
• Patients who have experienced progressive disease within 3 months of prior Bexxar or Zevalin
• Inability to understand or give an informed consent
• Central nervous system lymphoma
• Pregnancy
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
• Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) performance score > 2
• Eligible for radioimmunotherapy-based autologous transplant trial
• Medical condition that would contraindicate allogeneic transplantation
• Evidence of Human Anti-Mouse Antibody (HAMA) for patients with prior exposure to therapeutic murine antibodies
• Eligible for other therapeutic options that will be more likely to have a better long-term disease-free survival with lower potential toxicity (e.g., non-transplant therapy, autologous transplants, etc.) than this study
• Other grave medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g. unstable angina, pulmonary dysfunction [diffusing capacity of the lung for carbon monoxide (DLCO) < 30%, total lung capacity (TLC) < 30%, continuous supplemental oxygen], acquired immune deficiency syndrome [AIDS], etc.)
• DONOR: Identical twin
• DONOR: Age less than 12 years
• DONOR: Pregnancy
• DONOR: Infection with HIV
• DONOR: Inability to achieve adequate venous access
• DONOR: Known allergy to G-CSF
• DONOR: Current serious systemic illness or infection