A phase I trial of PS-341 and fludarabine for relapsed and refractory indolent non-Hodgkin’s lymphoma and chronic lymphocytic leukemia

7580 Background: The safety and efficacy of PS-341 (bortezomib) as a single agent in relapsed and refractory hematologic malignancies has been well documented. Fludarabine is known to be active in indolent non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). PS-341 may potentiate fludarabine activity by inhibiting DNA repair and inducing apoptosis in Bcl-2 over-expressing cells. The safety of this combination was evaluated in an ongoing phase I study. An additional dose level including rituxumab has been added to potentially improve efficacy without significant additional toxicity. Methods: Dose levels were as outlined in the table below. Each cycle was 21 days. Results: To date, 13 patients have received at least one cycle of treatment and are evaluable for toxicity. Diagnoses of patients included CLL, Waldenstom’s macroglobulinemia and MALT, lymphoplasmacytoid, mantle cell and follicular lymphomas. Patients received a median of 3 prior treatments (range 1–6). DLT’s were not observed in t...