A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia

Elias Jabbour, Nicholas J. Short, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G. Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M. Kadia, William G. Wierda, Courtney D. DiNardo, Mark Brandt, Susan M. O'BrienJorge E. Cortes, Hagop Kantarjian

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


BACKGROUND: Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS: Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine. RESULTS: The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P =.91), and the median overall survival was 24 months and not reached, respectively (P =.23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P =.32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P =.05] and 2-year overall survival rate: 72% vs 36% [P =.009]). CONCLUSIONS: CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9.

Original languageEnglish (US)
Pages (from-to)4430-4439
Number of pages10
Issue number22
StatePublished - Nov 15 2017
Externally publishedYes


  • acute myeloid leukemia
  • clofarabine
  • fludarabine
  • induction
  • nucleoside analog

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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