study of safety and efficacy of a sequential regimen consisting of three cycles of fludarabine followed by tositumomab and iodine i 131 tositumomab

Conditions: Lymphoma, Non-Hodgkin

Summary: this is a single-arm, single institution, phase ii study of fludarabine monophosphate followed by iodine i 131 tositumomab for patients with previously untreated, advanced-stage (stage iii or iv) low-grade, transformed low-grade and follicular non-hodgkin's lymphoma. the primary objective of the study will be to evaluate the safety of this treatment combination and the secondary endpoint will be to evaluate efficacy.


Eligibility criteria:
inclusion criteria: * patients must be age 18 years or older. * patients must have a histologically-confirmed diagnosis of low-grade or follicular non-hodgkin's b-cell lymphoma. * patients must have ann arbor stage iii or iv extent of disease after completing staging. * patients must have bi-dimensionally measurable disease. at least one lesion must have both perpendicular diameters \> 2 cm. * patients must have evidence that their tumor expresses the cd20 antigen by immunohistochemistry or flow cytometry. * patients must have no previous treatment for nhl. * patients must have a karnofsky performance status of at least 60% and an anticipated survival of at least 3 months. * patients must have absolute granulocyte count greater than or equal to 1500 cells/mm3 and a platelet count \> 100,000 cells/mm3 within 14 days of study entry and not require sustained support with hematopoietic cytokines or transfusion of blood products. * patients must have adequate renal and hepatic function. * patients must sign irb approved informed consent form(s) prior to study entry. exclusion criteria: * patients who received systemic steroids within 1 week of study entry, except patients on maintenance steroid therapy for a non-cancerous disease. * patients with evidence of active infection requiring intravenous antibiotics at the time of study entry. * patients with new york heart association class iii or iv heart disease or other serious illness that would preclude evaluation. * patients with known hiv infection. * patients with known brain or leptomeningeal metastases. * patients who are pregnant or nursing. patients of childbearing potential must undergo a pregnancy test at screening and on the day fludarabine treatment is started. treatment is not to be administered until a negative result is obtained. males and females must agree to use effective contraception for 6 months following the iodine i 131 tositumomab therapy. * patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years. * patients with hypersensitivity to fludarabine. * patients who are receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics. * patients who are hama positive. * patients with previous allergic reaction to iodine. this does not include reacting to intravenous iodine containing contrast materials. inclusion criteria for iodine i 131 tositumomab therapy * patients who completed 3 cycles of fludarabine. * patients must have absolute granulocyte count ≥ to 1500/mm3, platelet count of ≥ 100,000/mm3 (≥ 150,000/mm3 if \> 25% bone marrow involvement at restaging), and not require sustained support with hematopoietic cytokines or transfusions with blood products. * patients must have adequate renal and hepatic function. exclusion criteria for antibody therapy * patients with active obstructive hydronephrosis. * patients with evidence of active infection requiring intravenous antibiotics. * patients who are pregnant.