Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia

Richard M. Stone, Emanuele Mazzola, Donna Neuberg, Steven L. Allen, Arnaud Pigneux, Robert K. Stuart, Meir Wetzler, David Rizzieri, Harry P. Erba, Lloyd Damon, Jun Ho Jang, Martin S. Tallman, Krzysztof Warzocha, T. Masszi, Mikkael A. Sekeres, Miklos Egyed, Heinz August Horst, Dominik Selleslag, Scott R. Solomon, Parameswaran VenugopalAnte S. Lundberg, Bayard Powell

Research output: Article

32 Citations (Scopus)

Abstract

Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A +C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.

Original languageEnglish
Pages (from-to)1252-1257
Number of pages6
JournalJournal of Clinical Oncology
Volume33
Issue number11
DOIs
Publication statusPublished - márc. 20 2015

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amonafide
Daunorubicin
Cytarabine
Dilatation and Curettage
Acute Myeloid Leukemia
Drug Resistance
Intercalating Agents
Topoisomerase II Inhibitors
Therapeutics
Myelodysplastic Syndromes
Intravenous Infusions
Antineoplastic Agents
malic acid
Mortality
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. / Stone, Richard M.; Mazzola, Emanuele; Neuberg, Donna; Allen, Steven L.; Pigneux, Arnaud; Stuart, Robert K.; Wetzler, Meir; Rizzieri, David; Erba, Harry P.; Damon, Lloyd; Jang, Jun Ho; Tallman, Martin S.; Warzocha, Krzysztof; Masszi, T.; Sekeres, Mikkael A.; Egyed, Miklos; Horst, Heinz August; Selleslag, Dominik; Solomon, Scott R.; Venugopal, Parameswaran; Lundberg, Ante S.; Powell, Bayard.

In: Journal of Clinical Oncology, Vol. 33, No. 11, 20.03.2015, p. 1252-1257.

Research output: Article

Stone, RM, Mazzola, E, Neuberg, D, Allen, SL, Pigneux, A, Stuart, RK, Wetzler, M, Rizzieri, D, Erba, HP, Damon, L, Jang, JH, Tallman, MS, Warzocha, K, Masszi, T, Sekeres, MA, Egyed, M, Horst, HA, Selleslag, D, Solomon, SR, Venugopal, P, Lundberg, AS & Powell, B 2015, 'Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia', Journal of Clinical Oncology, vol. 33, no. 11, pp. 1252-1257. https://doi.org/10.1200/JCO.2014.57.0952
Stone, Richard M. ; Mazzola, Emanuele ; Neuberg, Donna ; Allen, Steven L. ; Pigneux, Arnaud ; Stuart, Robert K. ; Wetzler, Meir ; Rizzieri, David ; Erba, Harry P. ; Damon, Lloyd ; Jang, Jun Ho ; Tallman, Martin S. ; Warzocha, Krzysztof ; Masszi, T. ; Sekeres, Mikkael A. ; Egyed, Miklos ; Horst, Heinz August ; Selleslag, Dominik ; Solomon, Scott R. ; Venugopal, Parameswaran ; Lundberg, Ante S. ; Powell, Bayard. / Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 11. pp. 1252-1257.
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abstract = "Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46{\%} (99 of 216 patients) in A + C arm and 45{\%} (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19{\%} and 28{\%} in A +C arm and 13{\%} and 21{\%} in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.",
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T1 - Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia

AU - Stone, Richard M.

AU - Mazzola, Emanuele

AU - Neuberg, Donna

AU - Allen, Steven L.

AU - Pigneux, Arnaud

AU - Stuart, Robert K.

AU - Wetzler, Meir

AU - Rizzieri, David

AU - Erba, Harry P.

AU - Damon, Lloyd

AU - Jang, Jun Ho

AU - Tallman, Martin S.

AU - Warzocha, Krzysztof

AU - Masszi, T.

AU - Sekeres, Mikkael A.

AU - Egyed, Miklos

AU - Horst, Heinz August

AU - Selleslag, Dominik

AU - Solomon, Scott R.

AU - Venugopal, Parameswaran

AU - Lundberg, Ante S.

AU - Powell, Bayard

PY - 2015/3/20

Y1 - 2015/3/20

N2 - Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A +C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.

AB - Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A +C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.

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