Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR)

A randomised, controlled, double-blind, multinational, phase 3 study

Farhad Ravandi, Ellen K. Ritchie, Hamid Sayar, Jeffrey E. Lancet, Michael D. Craig, Norbert Vey, Stephen A. Strickland, Gary J. Schiller, Elias Jabbour, Harry P. Erba, Arnaud Pigneux, Heinz August Horst, Christian Recher, Virginia M. Klimek, Jorge Cortes, Gail J. Roboz, Olatoyosi Odenike, Xavier Thomas, Violaine Havelange, Johan Maertens & 16 others Hans Günter Derigs, Michael Heuser, Lloyd Damon, Bayard L. Powell, Gianluca Gaidano, Angelo Michele Carella, Andrew Wei, Donna Hogge, Adam R. Craig, Judith A. Fox, Renee Ward, Jennifer A. Smith, Gary Acton, Cyrus Mehta, Robert K. Stuart, Hagop M. Kantarjian

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Background: Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. Methods: This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m2 intravenously on days 1 and 4 in a first cycle; 70 mg/m2 in subsequent cycles) plus cytarabine (1 g/m2 intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Findings: Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355 patients, p

Original languageEnglish (US)
Article number169
Pages (from-to)1025-1036
Number of pages12
JournalThe Lancet Oncology
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2015

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Cytarabine
Acute Myeloid Leukemia
Placebos
Safety
vosaroxin
Anthraquinones
Induction Chemotherapy
Survival
Anthracyclines
Quinolones
Recurrence
Mortality

ASJC Scopus subject areas

  • Oncology

Cite this

Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR) : A randomised, controlled, double-blind, multinational, phase 3 study. / Ravandi, Farhad; Ritchie, Ellen K.; Sayar, Hamid; Lancet, Jeffrey E.; Craig, Michael D.; Vey, Norbert; Strickland, Stephen A.; Schiller, Gary J.; Jabbour, Elias; Erba, Harry P.; Pigneux, Arnaud; Horst, Heinz August; Recher, Christian; Klimek, Virginia M.; Cortes, Jorge; Roboz, Gail J.; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L.; Gaidano, Gianluca; Carella, Angelo Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R.; Fox, Judith A.; Ward, Renee; Smith, Jennifer A.; Acton, Gary; Mehta, Cyrus; Stuart, Robert K.; Kantarjian, Hagop M.

In: The Lancet Oncology, Vol. 16, No. 9, 169, 01.09.2015, p. 1025-1036.

Research output: Contribution to journalArticle

Ravandi, F, Ritchie, EK, Sayar, H, Lancet, JE, Craig, MD, Vey, N, Strickland, SA, Schiller, GJ, Jabbour, E, Erba, HP, Pigneux, A, Horst, HA, Recher, C, Klimek, VM, Cortes, J, Roboz, GJ, Odenike, O, Thomas, X, Havelange, V, Maertens, J, Derigs, HG, Heuser, M, Damon, L, Powell, BL, Gaidano, G, Carella, AM, Wei, A, Hogge, D, Craig, AR, Fox, JA, Ward, R, Smith, JA, Acton, G, Mehta, C, Stuart, RK & Kantarjian, HM 2015, 'Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): A randomised, controlled, double-blind, multinational, phase 3 study', The Lancet Oncology, vol. 16, no. 9, 169, pp. 1025-1036. https://doi.org/10.1016/S1470-2045(15)00201-6
Ravandi, Farhad ; Ritchie, Ellen K. ; Sayar, Hamid ; Lancet, Jeffrey E. ; Craig, Michael D. ; Vey, Norbert ; Strickland, Stephen A. ; Schiller, Gary J. ; Jabbour, Elias ; Erba, Harry P. ; Pigneux, Arnaud ; Horst, Heinz August ; Recher, Christian ; Klimek, Virginia M. ; Cortes, Jorge ; Roboz, Gail J. ; Odenike, Olatoyosi ; Thomas, Xavier ; Havelange, Violaine ; Maertens, Johan ; Derigs, Hans Günter ; Heuser, Michael ; Damon, Lloyd ; Powell, Bayard L. ; Gaidano, Gianluca ; Carella, Angelo Michele ; Wei, Andrew ; Hogge, Donna ; Craig, Adam R. ; Fox, Judith A. ; Ward, Renee ; Smith, Jennifer A. ; Acton, Gary ; Mehta, Cyrus ; Stuart, Robert K. ; Kantarjian, Hagop M. / Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR) : A randomised, controlled, double-blind, multinational, phase 3 study. In: The Lancet Oncology. 2015 ; Vol. 16, No. 9. pp. 1025-1036.
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TY - JOUR

T1 - Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR)

T2 - A randomised, controlled, double-blind, multinational, phase 3 study

AU - Ravandi, Farhad

AU - Ritchie, Ellen K.

AU - Sayar, Hamid

AU - Lancet, Jeffrey E.

AU - Craig, Michael D.

AU - Vey, Norbert

AU - Strickland, Stephen A.

AU - Schiller, Gary J.

AU - Jabbour, Elias

AU - Erba, Harry P.

AU - Pigneux, Arnaud

AU - Horst, Heinz August

AU - Recher, Christian

AU - Klimek, Virginia M.

AU - Cortes, Jorge

AU - Roboz, Gail J.

AU - Odenike, Olatoyosi

AU - Thomas, Xavier

AU - Havelange, Violaine

AU - Maertens, Johan

AU - Derigs, Hans Günter

AU - Heuser, Michael

AU - Damon, Lloyd

AU - Powell, Bayard L.

AU - Gaidano, Gianluca

AU - Carella, Angelo Michele

AU - Wei, Andrew

AU - Hogge, Donna

AU - Craig, Adam R.

AU - Fox, Judith A.

AU - Ward, Renee

AU - Smith, Jennifer A.

AU - Acton, Gary

AU - Mehta, Cyrus

AU - Stuart, Robert K.

AU - Kantarjian, Hagop M.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Background: Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. Methods: This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m2 intravenously on days 1 and 4 in a first cycle; 70 mg/m2 in subsequent cycles) plus cytarabine (1 g/m2 intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Findings: Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355 patients, p

AB - Background: Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. Methods: This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m2 intravenously on days 1 and 4 in a first cycle; 70 mg/m2 in subsequent cycles) plus cytarabine (1 g/m2 intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Findings: Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355 patients, p

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