Phase I dose escalation study of fludarabine, bortezomib, and rituximab for relapsed/refractory indolent and mantle cell non- Hodgkin lymphoma

8553 Background: Fludarabine (F) and bortezomib (B) have each demonstrated tolerability and efficacy in patients with non- Hodgkin lymphoma (NHL). Despite potential synergy between these agents, the combination remains untested. This phase I study was designed to obtain preliminary toxicity data and to determine the maximum tolerated dose (MTD) of the regimen. Methods: Relapsed or refractory indolent and mantle cell NHL and patients with chronic lymphocytic leukemia (CLL) were eligible. Dose levels of F and B were escalated as per the schema below with rituximab (R) being added to the 5th cohort. Due to unanticipated hematologic toxicity at dose level 5, cohorts 5a and 5b were subsequently added. Cycles were repeated every 21 days for a maximum of 8 cycles. Dose escalation occurred in cohorts of 3 patients. Cohorts were expanded to 6 patients if a dose limiting toxicity (DLT) was observed. The MTD was defined as one dose level below the cohort at which 1/3 of the patients experienced a DLT. Results: 23 pa...