This phase II trial studies the side effects and how well high-dose yttrium-90 (Y-90)-ibritumomab tiuxetan (anti-cluster of differentiation \[CD\]20) followed by fludarabine phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell transplant (PBSCT) work in treating patients with aggressive B-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Radiolabeled monoclonal antibodies, such as Y-90-ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them with less effect on normal cells. Giving chemotherapy, such as fludarabine phosphate, and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. However, high-dose radiolabeled antibodies also destroy healthy blood cells in the patient's body. When healthy stem cells from a donor are infused into the patient (stem cell transplant), they may help the patient's body replace these blood cells. Giving high-dose Y-90-ibritumomab tiuxetan followed by fludarabine phosphate, TBI, and donor PBSCT may be an effective treatment for patients with 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 up to 2 years thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)
Given PO
Given IV
Given IV
Given PO
Correlative studies
Given IV prior to yttrium Y 90 ibritumomab tiuxetan
Undergo TBI
Given IV
Given IV
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Progression-free Survival
Based on a one-sample chi-square test with one-sided significance level of five percent. This study will be deemed successful if the 1 year progression-free survival of this highest-risk group of patients is 54% or greater.
Time frame: 1 year
Absolute Neutrophil Count (ANC) Engraftment
The median time in days to achieve ANC recovery defined as ANC\>500uL.
Time frame: Up to day 100
Overall Survival
Time frame: Up to 2 years post transplant
Response Rates
Response is defined as having achieved a Partial Response or better.
Time frame: Day 100
Treatment-related Mortality
Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.
Time frame: Day 100
Platelet Engraftment
The median time in days to achieve platelet recovery as defined as platelet \>20,000uL.
Time frame: Up to day 100
Hematopoietic Toxicity
Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding.
Time frame: Up to day 100
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