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