A phase I trial of bortezomib in combination with fludarabine in patients with lymphoproliferative neoplasms

6647 Background: Bortezomib has been shown to be safe and effective single agent in the treatment of relapsed and refractory hematological malignancies. Fludarabine also is an active agent in treatment of indolent non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Bortezomib may potentiate fludarabine activity by inhibiting DNA repair and inducing apoptosis in Bcl-2 overexpressing cells. Methods: A phase I study combining bortezomib and fludarabine is being performed to determine the MTD/toxicities of this combination in patients with relapsed or refractory (progressive) indolent NHL or CLL. Cohorts of 3 patients received fludarabine 25mg/m2 days 1–3 and escalating doses of bortezomib on days 1,4,8 and 11 in 3 week cycles. Results: Thus far 7 patients (indolent NHL=4, CLL=2, Mantle Cell NHL=1) are evaluated in 3 of 4 planned dose cohorts of bortezomib (0.7, 1.0 and 1.3 mg/m2). All patients were treated with 2–6 prior regimens (median 4). A total of 27 cycles of therapy has been given and...