ORLANDO, Fla.—Pamela S. Becker, MD, PhD, at University of Washington in Seattle, Wash., and colleagues conducted a study that indicated priming with clofarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) (GCLAC) is active in relapsed and refractory acute myeloid leukemia (AML). Results of this study were presented at the 52nd American Society of Hematology Meeting and Exposition.

Clofarabine has been found to be active in both relapsed and newly diagnosed AML. It is more effective when used in combination with low-dose cytarabine. However, high-dose ara-C (HiDAC) is typically more effective than lower doses. The purpose of this study was to evaluate the combination of clofarabine and HiDAC with G-CSF priming in patients with relapsed AML or AML that failed to respond to initial therapy (refractory).

This was a phase 1, dose-escalation study in 50 patients (32 patients with relapsed AML and 18 with refractory AML). Treatment included clofarabine at 15 mg/m2, 20 mg/m2, or 25 mg/m2 daily for 5 days, in combination with cytarabine 2 g/m2 daily for 5 days, and G-CSF 5 g/kg subcutaneously, beginning 1 day before chemotherapy and continuing daily until neutrophil recovery (ANC>2). This was followed by a phase 2 expansion at the maximum tolerated dose (MTD) of 25 mg/m2. Complete response (CR) and survival rates in patients given GCLAC were compared with those seen in 101 relapsed/refractory patients given fludarabine 30 mg/m2 daily for 5 days and cytarabine 2 g/m2 daily for 5 days with G-CSF (FLAG, n=20) or without G-CSF (FA, n=81) in studies conducted prior to 2008.

Of the 50 patients enrolled in this study, 34 received GCLAC using clofarabine at the 25 mg/m2 MTD and 32 as first salvage therapy. The 46 evaluable patients had a CR of 46% (95% CI, 31-61%) and a CR + CRp (partial CR) rate of 61% (95% CI, 45-75%). Ninety percent of the CRs were observed after the first course of therapy. In those patients given a second induction course, the CR rate was 4/8. The median time to neutrophil count > 500 was 21 days (range, 17-39) and to platelet count > 100,000 was 30 days (range, 21-42). A 0% 30-day mortality rate was observed from day 1 of salvage induction chemotherapy. CR rates were also compared with those observed in patients treated with FA and FLAG at MD Anderson Cancer Center (MDACC). CR rates in patients treated with FA were 27% (22/81) and 16% with FLAG (3/19).

A multivariate analysis was conducted at MDACC showed that a greater overall survival rate with GCLAC compared to FA (HR 0.39, P<0.001) and FLAG (HR 0.58, P=0.09). Analysis by the Fred Hutchinson Cancer Research Center (FHCRC) indicated GCLAC to be associated with higher CR rates than FA or FLAG (P<0.0001 and P=0.0008, respectively) and longer survival than FA (P=0.001).

Grade ≥ 3 toxicity was similar to that seen with other HiDAC regimens. The most frequent adverse events were infections and pulmonary toxicity (invariably associated with infection) occurring in 40% and 46% of patients, respectively.

The results of this study indicate that GCLAC is active in patients with relapsed and refractory AML. However, additional studies comparing GCLAC to other regimens like FLAG are warranted.