Phase I/II trial of clofarabine in refractory and/or relapsed non-hodgkin’s lymphoma (NHL)

Abstract

8564 Background: Clofarabine (CLO) is a second generation nucleoside analogue with known activity in acute leukemia and myelodysplasia. Given the lack of standard therapy in refractory and transplant-ineligible relapsed NHL, we investigated the activity of CLO in this patient (pt) population regardless of histology. Methods: Eligible pts had relapsed and/or refractory NHL with measurable disease, ECOG performance status ≤ 2, and adequate renal, cardiac, liver, and bone marrow function (unless cytopenias were disease- related). CLO was given intravenously over 1-hour days 1–5 every 28 days for 6 cycles maximum. All pts received anti-viral and anti- pneumocystis carinii prophylaxis. A standard 3x3 phase I study design was used with CLO 4 mg/m2 in cohort 1 and subsequent cohorts escalated by 2 mg/m2. Once the maximum tolerated dose (MTD) was determined, the phase II portion of this study was initiated at the MTD. All pts were followed until disease progression. Results: To date, 14 pts have been enrolled with 7 patients each in the phase I and II portions. Including all pts, median age was 78 years (27–84), median number of prior therapies was 2.5 (1–8), and 3 pts (21%) relapsed after autologous stem cell transplantation. Histologies included 4 diffuse large cell, 3 small lymphocytic, 2 anaplastic large cell, 2 mixed large cell/follicular, 1 follicular, 1 refractory marginal zone, and 1 Richter’s transformation. Median CLO cycles were 2.5 (1–6). Grade 3/4 non-hematologic toxicities were: 1 (7%) grade 3 pleural effusion and 2 (14%) grade 3 fatigue. All pts required growth factor support and 2 pts on the phase II portion required a dose reduction. Thrombocytopenia was the dose-limiting toxicity at 6 mg/m2 in 2/6 patients. The MTD and recommended phase II dose was 4 mg/m2. Responses: 2 (14%) complete responses lasting 4 and 12+ months, 3 (21%) partial responses, 1 minor response, and 1 stable disease. The overall response rate was 35% for this heavily pretreated pt population. With a median follow up of 5 months (1–13), the median duration of response has not been reached and 6 patients remain alive (42%). Conclusions: To our knowledge, this is the first report to establish clinical activity with CLO in refractory and/or relapsed NHL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genzyme Genzyme