Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia

Aziz Nazha, Hagop Kantarjian, Farhad Ravandi, Xuelin Huang, Sangbum Choi, Guillermo Garcia-Manero, Elias Jabbour, Gautam Borthakur, Tapan Kadia, Marina Konopleva, Jorge Cortes, Alessandra Ferrajoli, Steve Kornblau, Naval Daver, Naveen Pemmaraju, Michael Andreeff, Zeev Estrov, Min Du, Mark Brandt, Stefan Faderl

Research output: Contribution to journalArticle

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. Am. J. Heamtol. 88:961-966, 2013.

Original languageEnglish (US)
Pages (from-to)961-966
Number of pages6
JournalAmerican Journal of Hematology
Volume88
Issue number11
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

Fingerprint

Idarubicin
Cytarabine
Acute Myeloid Leukemia
Disease-Free Survival
Therapeutics
Survival
clofarabine
Nucleosides
Multivariate Analysis

ASJC Scopus subject areas

  • Hematology

Cite this

Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. / Nazha, Aziz; Kantarjian, Hagop; Ravandi, Farhad; Huang, Xuelin; Choi, Sangbum; Garcia-Manero, Guillermo; Jabbour, Elias; Borthakur, Gautam; Kadia, Tapan; Konopleva, Marina; Cortes, Jorge; Ferrajoli, Alessandra; Kornblau, Steve; Daver, Naval; Pemmaraju, Naveen; Andreeff, Michael; Estrov, Zeev; Du, Min; Brandt, Mark; Faderl, Stefan.

In: American Journal of Hematology, Vol. 88, No. 11, 01.11.2013, p. 961-966.

Research output: Contribution to journalArticle

Nazha, A, Kantarjian, H, Ravandi, F, Huang, X, Choi, S, Garcia-Manero, G, Jabbour, E, Borthakur, G, Kadia, T, Konopleva, M, Cortes, J, Ferrajoli, A, Kornblau, S, Daver, N, Pemmaraju, N, Andreeff, M, Estrov, Z, Du, M, Brandt, M & Faderl, S 2013, 'Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia', American Journal of Hematology, vol. 88, no. 11, pp. 961-966. https://doi.org/10.1002/ajh.23544
Nazha, Aziz ; Kantarjian, Hagop ; Ravandi, Farhad ; Huang, Xuelin ; Choi, Sangbum ; Garcia-Manero, Guillermo ; Jabbour, Elias ; Borthakur, Gautam ; Kadia, Tapan ; Konopleva, Marina ; Cortes, Jorge ; Ferrajoli, Alessandra ; Kornblau, Steve ; Daver, Naval ; Pemmaraju, Naveen ; Andreeff, Michael ; Estrov, Zeev ; Du, Min ; Brandt, Mark ; Faderl, Stefan. / Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. In: American Journal of Hematology. 2013 ; Vol. 88, No. 11. pp. 961-966.
@article{a136034a17614286ae0d287a329876e0,
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. Am. J. Heamtol. 88:961-966, 2013.",
author = "Aziz Nazha and Hagop Kantarjian and Farhad Ravandi and Xuelin Huang and Sangbum Choi and Guillermo Garcia-Manero and Elias Jabbour and Gautam Borthakur and Tapan Kadia and Marina Konopleva and Jorge Cortes and Alessandra Ferrajoli and Steve Kornblau and Naval Daver and Naveen Pemmaraju and Michael Andreeff and Zeev Estrov and Min Du and Mark Brandt and Stefan Faderl",
year = "2013",
month = "11",
day = "1",
doi = "10.1002/ajh.23544",
language = "English (US)",
volume = "88",
pages = "961--966",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "11",

}

TY - JOUR

T1 - Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia

AU - Nazha, Aziz

AU - Kantarjian, Hagop

AU - Ravandi, Farhad

AU - Huang, Xuelin

AU - Choi, Sangbum

AU - Garcia-Manero, Guillermo

AU - Jabbour, Elias

AU - Borthakur, Gautam

AU - Kadia, Tapan

AU - Konopleva, Marina

AU - Cortes, Jorge

AU - Ferrajoli, Alessandra

AU - Kornblau, Steve

AU - Daver, Naval

AU - Pemmaraju, Naveen

AU - Andreeff, Michael

AU - Estrov, Zeev

AU - Du, Min

AU - Brandt, Mark

AU - Faderl, Stefan

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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. Am. J. Heamtol. 88:961-966, 2013.

AB - 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. Am. J. Heamtol. 88:961-966, 2013.

UR - http://www.scopus.com/inward/record.url?scp=84886286103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886286103&partnerID=8YFLogxK

U2 - 10.1002/ajh.23544

DO - 10.1002/ajh.23544

M3 - Article

C2 - 23877926

AN - SCOPUS:84886286103

VL - 88

SP - 961

EP - 966

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 11

ER -