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 journalArticle

Abstract

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
JournalCancer
Volume123
Issue number22
DOIs
StatePublished - Nov 15 2017
Externally publishedYes

Fingerprint

Idarubicin
Cytarabine
Acute Myeloid Leukemia
Disease-Free Survival
Survival Rate
Purine Nucleosides
clofarabine
fludarabine
Hyperbilirubinemia
Survival
Mortality
Transaminases
Exanthema
Blood Platelets
Safety
Drug Therapy

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jabbour, E., Short, N. J., Ravandi, F., Huang, X., Xiao, L., Garcia-Manero, G., ... Kantarjian, H. (2017). A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer, 123(22), 4430-4439. https://doi.org/10.1002/cncr.30883

A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. / Jabbour, Elias; Short, Nicholas J.; Ravandi, Farhad; Huang, Xuelin; Xiao, Lianchun; Garcia-Manero, Guillermo; Plunkett, William; Gandhi, Varsha; Sasaki, Koji; Pemmaraju, Naveen; Daver, Naval G.; Borthakur, Gautam; Jain, Nitin; Konopleva, Marina; Estrov, Zeev; Kadia, Tapan M.; Wierda, William G.; DiNardo, Courtney D.; Brandt, Mark; O'Brien, Susan M.; Cortes, Jorge E.; Kantarjian, Hagop.

In: Cancer, Vol. 123, No. 22, 15.11.2017, p. 4430-4439.

Research output: Contribution to journalArticle

Jabbour, E, Short, NJ, Ravandi, F, Huang, X, Xiao, L, Garcia-Manero, G, Plunkett, W, Gandhi, V, Sasaki, K, Pemmaraju, N, Daver, NG, Borthakur, G, Jain, N, Konopleva, M, Estrov, Z, Kadia, TM, Wierda, WG, DiNardo, CD, Brandt, M, O'Brien, SM, Cortes, JE & Kantarjian, H 2017, 'A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia', Cancer, vol. 123, no. 22, pp. 4430-4439. https://doi.org/10.1002/cncr.30883
Jabbour, Elias ; Short, Nicholas J. ; Ravandi, Farhad ; Huang, Xuelin ; Xiao, Lianchun ; Garcia-Manero, Guillermo ; Plunkett, William ; Gandhi, Varsha ; Sasaki, Koji ; Pemmaraju, Naveen ; Daver, Naval G. ; Borthakur, Gautam ; Jain, Nitin ; Konopleva, Marina ; Estrov, Zeev ; Kadia, Tapan M. ; Wierda, William G. ; DiNardo, Courtney D. ; Brandt, Mark ; O'Brien, Susan M. ; Cortes, Jorge E. ; Kantarjian, Hagop. / A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. In: Cancer. 2017 ; Vol. 123, No. 22. pp. 4430-4439.
@article{35aa364c077e4a8b8b72b78d0d963848,
title = "A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia",
abstract = "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.",
keywords = "acute myeloid leukemia, clofarabine, fludarabine, induction, nucleoside analog",
author = "Elias Jabbour and Short, {Nicholas J.} and Farhad Ravandi and Xuelin Huang and Lianchun Xiao and Guillermo Garcia-Manero and William Plunkett and Varsha Gandhi and Koji Sasaki and Naveen Pemmaraju and Daver, {Naval G.} and Gautam Borthakur and Nitin Jain and Marina Konopleva and Zeev Estrov and Kadia, {Tapan M.} and Wierda, {William G.} and DiNardo, {Courtney D.} and Mark Brandt and O'Brien, {Susan M.} and Cortes, {Jorge E.} and Hagop Kantarjian",
year = "2017",
month = "11",
day = "15",
doi = "10.1002/cncr.30883",
language = "English (US)",
volume = "123",
pages = "4430--4439",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "22",

}

TY - JOUR

T1 - A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia

AU - Jabbour, Elias

AU - Short, Nicholas J.

AU - Ravandi, Farhad

AU - Huang, Xuelin

AU - Xiao, Lianchun

AU - Garcia-Manero, Guillermo

AU - Plunkett, William

AU - Gandhi, Varsha

AU - Sasaki, Koji

AU - Pemmaraju, Naveen

AU - Daver, Naval G.

AU - Borthakur, Gautam

AU - Jain, Nitin

AU - Konopleva, Marina

AU - Estrov, Zeev

AU - Kadia, Tapan M.

AU - Wierda, William G.

AU - DiNardo, Courtney D.

AU - Brandt, Mark

AU - O'Brien, Susan M.

AU - Cortes, Jorge E.

AU - Kantarjian, Hagop

PY - 2017/11/15

Y1 - 2017/11/15

N2 - 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.

AB - 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.

KW - acute myeloid leukemia

KW - clofarabine

KW - fludarabine

KW - induction

KW - nucleoside analog

UR - http://www.scopus.com/inward/record.url?scp=85023622400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023622400&partnerID=8YFLogxK

U2 - 10.1002/cncr.30883

DO - 10.1002/cncr.30883

M3 - Article

C2 - 28708931

AN - SCOPUS:85023622400

VL - 123

SP - 4430

EP - 4439

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 22

ER -