title: Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia.
abstract: Clofarabine is a second generation nucleoside analogue with activity in adults with acute myeloid leukemia (AML). A phase I trial of clofarabine, idarubicin, and cytarabine (CIA) in relapsed and refractory AML had shown an overall response rate (ORR) of 48%. To explore this combination further, we conducted a phase II study of (CIA) in patients with newly diagnosed AML ≤60 years. Patients ≥18-60 years with AML and adequate organ function were enrolled. Induction therapy consisted of clofarabine (C) 20 mg m⁻² IV daily (days 1-5), idarubicin (I) 10 mg m⁻² IV daily (days 1-3), and cytarabine (A) 1 g m⁻² IV daily (days 1-5). Patients in remission received up to six consolidation cycles (C 15 mg m⁻² × 3, I 8 mg m⁻² × 2, and A 0.75 g m⁻² × 3). Fifty-seven patients were evaluable. ORR was 79%. With a median follow up of 10.9 months, the median overall survival (OS) was not reached, the median event-free survival (EFS) was 13.5 months. Most toxicities were ≤grade 2. Four week mortality was 2%. In subgroup analysis, patients ≤40 years had better OS (P = 0.04) and EFS (P = 0.04) compared to patients >40 years. Compared to historical patients treated with idarubicin and cyarabine (IA), the OS and EFS were significantly longer for CIA treated patients. In multivariate analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an effective and safe therapy for patients ≤60 years with newly diagnosed AML.
authors.affiliation: Department of Leukemia, The University of Texas-M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Aziz
authors.initials: A
authors.lastname: Nazha
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Xuelin
authors.initials: X
authors.lastname: Huang
authors.forename: Sangbum
authors.initials: S
authors.lastname: Choi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Steve
authors.initials: S
authors.lastname: Kornblau
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Min
authors.initials: M
authors.lastname: Du
authors.forename: Mark
authors.initials: M
authors.lastname: Brandt
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077866:Clofarabine; D060830:Consolidation Chemotherapy / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003875:Drug Eruptions / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060828:Induction Chemotherapy / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010865:Pilot Projects; D012074:Remission Induction; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine; D015255:Idarubicin