High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

PRIMARY OBJECTIVES:

I. To assess the safety and efficacy of 1.5 mCi/kg (max 120 mCi) 90Y-Ibritumomab tiuxetan
(yttrium Y 90 ibritumomab tiuxetan) (anti-CD20) combined with fludarabine (fludarabine
phosphate) (30 mg/m^2 x 3) and 2 gray (Gy) total body irradiation followed by human leukocyte
antigens (HLA) matched allogeneic hematopoietic transplantation for patients with relapsed or
refractory aggressive B-cell lymphoma.

OUTLINE:

Beginning 24-48 hours prior to therapy infusion, patients receive rituximab intravenously
(IV) over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab
tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine
phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients
also receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 with taper to day
180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate
mofetil PO BID on days 0-27 (related donor) or PO thrice daily (TID) on days 0-40 with taper
to day 96 (unrelated donor).

After completion of study treatment and assessments through ~day 100 following transplant,
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 aggressive B-cell lymphoma
(diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], etc.) expressing the
CD20 antigen and have failed at least one prior standard systemic therapy

- Patients must have relapsed after high-dose therapy and autologous transplantation or
be ineligible for high-dose therapy and autologous transplantation; patients that have
failed autologous transplantation are those with persistent disease > 30 days after
transplant; those ineligible for autologous transplant include those with
chemoresistant disease (i.e., patients who have not achieved a partial response or
better with their most recent chemotherapy regimen), are expected to have a poor
outcome from autologous transplant (e.g., DLBCL relapsing within one year of
rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate,
prednisone [R-CHOP]-like chemotherapy, double hit lymphoma, v-myc myelocytomatosis
viral oncogene homolog (avian) positive [MYC+] lymphoma, persistent positron emission
tomography [PET] positivity after chemotherapy), are unable to collect sufficient or
tumor-free autologous stem cells per Seattle Cancer Care Alliance (SCCA) standard
practice, are unable to tolerate the high-dose autologous conditioning regimens, or
who refuse a high-dose autologous transplant regimen

- Creatinine (Cr) < 2.0

- Bilirubin < 1.5 mg/dL with the exception of patients thought to have Gilbert's
syndrome, who may have a total bilirubin above 1.5 mg/dL

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of
normal (ULN)

- Patients must have an expected survival without treatment of > 60 days and must be
free of major infection including human immunodeficiency virus (HIV)

- Patients must have an HLA-identical related or HLA-matched unrelated donor

Exclusion Criteria:

- Receipt of systemic anti-lymphoma therapy withinthe following intervals prior to the
therapeutic 90Y-ibritumomab tiuxetan dose:

- < 30 days for intravenously-administered cytotoxic chemotherapy and/or monoclonal
antibodies

- < 5 half-lives for all other anti-cancer agents (e.g., targeted therapies,
corticosteroids, immunomodulatory agents, etc.)

- Inability to understand or give an informed consent

- Active 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

- High-dose chemotherapy or external beam radiation therapy to lung, liver, or kidneys >
20 Gy within the previous 100 days prior to therapeutic 90Y-ibritumomab tiuxetan dose

- Medical condition that would contraindicate allogeneic transplantation as per standard
practice guidelines (e.g., impaired cardiopulmonary function, hepatitis, etc)