Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia

Abstract

Clofarabine has shown activity and tolerability in older patients with acute myeloid leukemia (AML). We investigated the safety and tolerability of an oral formulation of clofarabine for consolidation therapy of patients aged 60 and older with AML. In this phase I study, twenty-two patients older than 60 years with AML in first complete remission were treated once daily with oral clofarabine for 14 or 21 days of a 28 day cycle, for up to 5 cycles. Dose escalation from 1 mg to 6 mg daily using a 3 + 3 design was used to determine dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and tolerability of oral clofarabine. No DLTs or Grade 3-4 nonhematologic toxicities were observed. The primary toxicities were hematologic, including uncomplicated grade 3-4 neutropenia (50%) and thrombocytopenia (50%). Given that myelosuppression necessitating dose delays/reductions was observed more commonly at higher doses, the recommended phase II dose is 2 mg daily for 21 of 28 days. At doses equal to or greater than 2 mg, the median relapse-free survival was 28.35 months. Oral clofarabine was well-tolerated with encouraging activity in patients older than 60 years. Further investigation of oral clofarabine as a consolidation and/or maintenance therapy in AML for older individuals is warranted. (ClinicalTrials.gov:NCT00727766).

Dual anti-HIV mechanism of clofarabine

“…Hydroxyurea and clofarabine differ greatly in structure and in the mechanism of RNR inhibition. Clofarabine has been used as a second line cancer treatment since its FDA approval in 2004 and recent trials have had positive results using it as a first line cancer treatment that can be administered orally [ 41 , 42 ]. Any use of clofarabine as an HIV drug would require further drug interaction studies to establish the safety of clofarabine both alone and with commonly used combination therapies.…”

Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective

“…In several comparable studies, the efficacy of clofarabine was measured in AML patients. Megan and colleagues [84] analyzed 22 patients who were 60 years or older. Clofarabine dose ranged from 1 to 6 mg and was given to patients once daily for 14 or 21 days of a 28-day cycle, and the adverse effects of clofarabine were evaluated.…”