title: Clofarabine combinations as acute myeloid leukemia salvage therapy.
abstract: BACKGROUND
  Outcome of patients with relapsed acute myeloid leukemia (AML) remains unsatisfactory. Clofarabine is a nucleoside analog with activity in adult AML. Combinations with cytarabine in AML are feasible and effective. Idarubicin is another active AML drug, which has not yet been tested with clofarabine.
  
  
  METHODS
  The authors therefore designed a phase I study of clofarabine +/- cytarabine, plus idarubicin. Patients with primary refractory or first-relapse AML were assigned to either clofarabine plus idarubicin (CI) if previously exposed to cytarabine with a response lasting <12 months, or clofarabine and idarubicin plus cytarabine (CIA) for responses > or = 12 months, or if never exposed to cytarabine. A standard "3 + 3" phase 1 design was followed to define maximum tolerated dose (MTD). Forty-four patients were treated (23 CI; 21 CIA).
  
  
  RESULTS
  Dose-limiting toxicities were hyperbilirubinemia and hepatic transaminase elevations for CI-treated patients in addition to mucositis and diarrhea for CIA-treated patients. MTD for CI was clofarabine 22.5 mg/m(2) intravenously daily x 5 and idarubicin 10 mg/m(2) intravenously daily x 3. MTD for CIA was clofarabine 22.5 mg/m(2) intravenously x 5, idarubicin 6 mg/m(2) intravenously x 3, and cytarabine 0.75 g/m(2) intravenously x 5 days.
  
  
  CONCLUSIONS
  A phase 2 randomized trial is in process to compare activity between treatment arms.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. sfaderl@mdanderson.org
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Xuelin
authors.initials: X
authors.lastname: Huang
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Monica
authors.initials: M
authors.lastname: Kwari
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian