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

Meagan A. Jacoby, Michael Martin, Geoffrey L. Uy, Peter Westervelt, John F. Dipersio, Amanda Cashen, Keith Stockerl-Goldstein, Ravi Vij, Jingqin Luo, Teresa Reineck, Noel Bernabe, Camille N. Abboud

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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 five 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.

Original languageEnglish (US)
Pages (from-to)487-492
Number of pages6
JournalAmerican Journal of Hematology
Volume89
Issue number5
DOIs
StatePublished - Jan 1 2014

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Acute Myeloid Leukemia
Maximum Tolerated Dose
Neutropenia
Thrombocytopenia
clofarabine
Safety
Recurrence
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia. / Jacoby, Meagan A.; Martin, Michael; Uy, Geoffrey L.; Westervelt, Peter; Dipersio, John F.; Cashen, Amanda; Stockerl-Goldstein, Keith; Vij, Ravi; Luo, Jingqin; Reineck, Teresa; Bernabe, Noel; Abboud, Camille N.

In: American Journal of Hematology, Vol. 89, No. 5, 01.01.2014, p. 487-492.

Research output: Contribution to journalArticle

Jacoby, MA, Martin, M, Uy, GL, Westervelt, P, Dipersio, JF, Cashen, A, Stockerl-Goldstein, K, Vij, R, Luo, J, Reineck, T, Bernabe, N & Abboud, CN 2014, 'Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia', American Journal of Hematology, vol. 89, no. 5, pp. 487-492. https://doi.org/10.1002/ajh.23663
Jacoby, Meagan A. ; Martin, Michael ; Uy, Geoffrey L. ; Westervelt, Peter ; Dipersio, John F. ; Cashen, Amanda ; Stockerl-Goldstein, Keith ; Vij, Ravi ; Luo, Jingqin ; Reineck, Teresa ; Bernabe, Noel ; Abboud, Camille N. / Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia. In: American Journal of Hematology. 2014 ; Vol. 89, No. 5. pp. 487-492.
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