Clofarabine plus cytarabine (ara-C) is an active induction regimen for newly diagnosed patients (pts) ≥ age 50 with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS)

Abstract

6609 Background: Clofarabine is a new-generation nucleoside analog with activity in acute leukemias. As a potent inhibitor of ribonucleotide reductase, it is also suited for biochemical modulation strategies with other nucleoside analogs. In a phase I/II study of clofarabine + ara-C in pts with relapsed/refractory AML/MDS, we reported a response rate of 41% (24% CR, 17% CRp) (Blood 102:615a, 2003). Cellular pharmacology studies suggested that accumulation of intracellular clofarabine triphosphate resulted in higher ara-CTP accumulation of the leukemia blasts. Methods: We are conducting a phase II study of clofarabine + ara-C to evaluate efficacy and safety of this combination in pts ≥ 50 years (yrs) with newly diagnosed AML and high-risk MDS (≥ 10% marrow blasts). Pts with good prognosis karyotypes [t(8;21), inv(16), t(15;17)], ECOG PS > 2, and age ≥ 75 are excluded. Clofarabine is given at 40mg/m2/d as a 1-hour (hr) i.v. infusion for 5 days (d2–6) followed 4 hrs later by ara-C at 1g/m2/d as a 2-hr i.v. infusion for 5 days (d1–5). Results: 31 (28 AML, 3 MDS) of 37 pts are evaluable. Median age 61 yrs (range 50–72). Cytogenetics: diploid in 16 and abnormal in 15 pts. Median WBC 9.1 x 109/L (1–135.8). Median platelet count 44 x 109/L (8–871). 16 pts (52%) achieved CR after one induction course; another 4 pts (13%) achieved CRp. Of 6 pts who received a second induction course, one pt (CRp) responded. The CR rate was 63% (10/16 pts) in the diploid and 40% (6/15) in the abnormal group. Median time to CR: 28 days (23–56). 4 pts (13%) died on study: 1 pt died on d35 of complications due to sepsis; the remaining 3 pts died following a second induction course (d 47, 52, 78) due to prolonged cytopenias and sepsis. Clofarabine infusion related adverse events included facial flushing and headaches (< gr. 3) and were transient. Other toxicities included hyperbilirubinemia (gr. 3 in 3 pts) and pancreatitis (1 pt). Conclusions: The combination of clofarabine + ara-C is active in older pts with newly diagnosed AML/high-risk MDS. The toxicity profile is acceptable. An update of response and toxicity data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ILEX ILEX Oncology ILEX Oncology