Randomized phase II study of clofarabine versus clofarabine plus low-dose cytarabine (ara-C) for patients (pts) ≥ 60 years (yrs) with newly diagnosed acute myeloid leukemia (AML)

Abstract

6627 Background: Outcome of pts ≥ 60 yrs with AML remains poor. Although response rates with standard chemotherapy may exceed 50%, toxicity is substantial, relapse rates are high, and long-term DFS is rare. Clofarabine is a next-generation nucleoside analog with activity in AML. In a recent trial of clofarabine + intermediate dose ara-C for pts ≥ 50 yrs with newly diagnosed AML, we have reported a 60% OR (51% CR) rate with a low induction mortality of 7% (Blood 2004; 104: abs #875). Here we report preliminary results of a lower dose schedule of clofarabine +/- low-dose ara-C (LDAC) in pts ≥ 60 yrs with AML. Methods: Pts with untreated AML are randomized to induction therapy with either clofarabine alone (clofarabine 30mg/m2/d i.v. d1–5) or clofarabine plus LDAC (clofarabine 30mg/m2/d i.v. d1–5 + ara-C 20mg/m2/d s.c. d1–14). Pts in remission receive consolidation therapy q4–7 wks with clofarabine administered on d1–3 and LDAC on d1–7 per course, respectively. Pts are excluded for ECOG PS > 2 and a history of NYHA grade 3 heart disease. Randomization of pts will be adaptive after the first 20 pts have been randomized with equal probability to either arm and have been evaluated for response. Primary endpoints include evaluation of efficacy (CR rate, CR duration) and tolerability. Results: Fourteen pts have been enrolled (7 in each arm) of whom 10 are evaluable for response. Median age: 72 yrs (range 60–83). Five pts (50%) had secondary AML with an antecedent hematologic disorder (AHD) and 5 pts (50%) had abnormal cytogenetics. Seven pts (70%) achieved CR after one course (4 of 5 on clofarabine and 3 of 5 on clofarabine + LDAC). Median time to CR: 33 days (25–47). Four CR pts (57%) had abnormal cytogenetics and 3 (43%) had AHD. Two pts (20%) experienced early death, which was not considered related to study drugs: 71 yo female with E. coli sepsis on d12 (clofarabine); 83 yo male with pulmonary hemorrhage and pneumonia d14 (clofarabine + LDAC). Conclusions: Both clofarabine and clofarabine + LDAC are active in older pts with AML. Although the toxicity profile is favorable, myelosuppression is common. An update of responses and toxicity profile will be presented. No significant financial relationships to disclose.