Clofarabine Is Active in Myelodysplastic Syndrome (MDS).

Background. Clofarabine, an adenosine nucleoside analog, is active in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Its anti-MDS activity is not well defined.

Study Aims. To evaluate the safety and efficacy of clofarabine in MDS in two studies, one with intravenous administration and one with oral, using lower doses than those for leukemia (40–52 mg/m² IV daily x 5).

Study Group and Results. The first study randomized patients in a Bayesian design to receive clofarabine 15 or 30 mg/m² IV daily x 5 every 4–6 weeks. The second study used clofarabine 40 mg/m² orally daily x 5 every 4–6 weeks (assuming oral bioavailability about 50%). Standard eligibility criteria for MDS were used; only high risk MDS patients (IPSS intermediate or high) were eligible. So far, 16 patients have been treated, 10 on IV clofarabine and 6 on oral clofarabine. Age ≥60 yr in 13 (81%); prior therapy with decitabine/azacitidine 11 (69%); cytogenetic abnormalities 12 (75%). Responses were graded according to International Working Group criteria (IWG). Results are shown in the table below.

Myelosuppression was significant resulting in febrile episodes and hospitalization in 4/6 patients on oral clofarabine and in 4/10 patients on IV clofarabine. Rash grade 3 was noted in 1 patient on oral clofarabine.

Summary. Clofarabine is active in MDS. The oral dose of 40 mg/m² daily x 5 may be too high for MDS; lower dose of oral clofarabine 30 mg/m² orally daily x 5 will be tested with PK studies. The 2 IV schedules (15 vs. 30 mg/m²) are ongoing.