Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma

OBJECTIVES: Primary * To compare the progression-free survival (PFS) of patients with relapsed or refractory indolent non-Hodgkin lymphoma treated with fludarabine phosphate and rituximab with vs without pixantrone. Secondary * To compare the overall objective response rate (complete response \[CR\], unconfirmed complete response \[CRu\], and partial response \[PR\]) in these patients. * To compare the CR and CRu rate in these patients. * To compare the duration of response and time to progression in these patients. * To compare the overall survival and disease-specific survival of these patients. * To compare the safety (including cardiac safety) and tolerability of these regimens in these patients. OUTLINE: This is a multicenter study. Patients are stratified by Follicular Lymphoma International Prognostic Index (FLIPI) score (0 or 1 vs ≥ 2), number of prior treatments (1 or 2 vs \> 2), and prior anti-CD20 regimen (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I (control): Patients receive rituximab IV on day 1 and fludarabine phosphate IV on days 2-4. Treatment repeats every 28 days for up to 6 courses\* in the absence of unacceptable toxicity or disease progression. * Arm II: Patients receive rituximab and fludarabine phosphate as in arm I. Patients also receive pixantrone IV on day 2. Treatment repeats every 28 days for up to 6 courses\* in the absence of unacceptable toxicity or disease progression. NOTE: \*Only patients achieving complete response, unconfirmed complete response, or partial response after 4 courses receive courses 5 and 6. After completion of study therapy, patients are followed periodically for up to 5 years.