A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease

Mark R. Litzow, Xin V. Wang, Martin P. Carroll, Judith E. Karp, Rhett P. Ketterling, Yanming Zhang, Scott H. Kaufmann, Hillard M. Lazarus, Selina M. Luger, Elisabeth M. Paietta, Keith W. Pratz, Han Win Tun, Jessica K Altman, Edward R. Broun, Witold B. Rybka, Jacob M. Rowe, Martin S. Tallman

Research output: Contribution to journalArticle

Abstract

To improve the outcome of relapsed/refractory acute myeloid leukemia (AML), a randomized phase II trial of three novel regimens was conducted. Ninety patients were enrolled and were in first relapse or were refractory to induction/re-induction chemotherapy. They were randomized to the following regimens: carboplatin-topotecan (CT), each by continuous infusion for 5 days; alvocidib (formerly flavopiridol), cytarabine, and mitoxantrone (FLAM) in a timed sequential regimen; or sirolimus combined with mitoxantrone, etoposide, and cytarabine (S-MEC). The primary objective was attainment of a complete remission (CR). A Simon two-stage design was used for each of the three arms. The median age of the patients in the FLAM arm was older at 62 years compared with 55 years for the CT arm and the S-MEC arm. The overall response was 14% in the CT arm (5/35, 90% CI 7%-35%), 28% in the FLAM arm (10/36, 90% CI, 16%-43%), and 16% in the S-MEC arm (3/19, 90% CI, 4%-36%). There were nine treatment-related deaths, seven of which occurred in the FLAM arm with four of these in elderly patients. We conclude that the FLAM regimen had an encouraging response rate and should be considered for further clinical development but should be used with caution in elderly patients.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalAmerican Journal of Hematology
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2019

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alvocidib
Mitoxantrone
Cytarabine
Acute Myeloid Leukemia
Topotecan
Carboplatin
Induction Chemotherapy
Etoposide
Sirolimus

ASJC Scopus subject areas

  • Hematology

Cite this

Litzow, Mark R. ; Wang, Xin V. ; Carroll, Martin P. ; Karp, Judith E. ; Ketterling, Rhett P. ; Zhang, Yanming ; Kaufmann, Scott H. ; Lazarus, Hillard M. ; Luger, Selina M. ; Paietta, Elisabeth M. ; Pratz, Keith W. ; Tun, Han Win ; Altman, Jessica K ; Broun, Edward R. ; Rybka, Witold B. ; Rowe, Jacob M. ; Tallman, Martin S. / A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease. In: American Journal of Hematology. 2019 ; Vol. 94, No. 1. pp. 111-117.
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abstract = "To improve the outcome of relapsed/refractory acute myeloid leukemia (AML), a randomized phase II trial of three novel regimens was conducted. Ninety patients were enrolled and were in first relapse or were refractory to induction/re-induction chemotherapy. They were randomized to the following regimens: carboplatin-topotecan (CT), each by continuous infusion for 5 days; alvocidib (formerly flavopiridol), cytarabine, and mitoxantrone (FLAM) in a timed sequential regimen; or sirolimus combined with mitoxantrone, etoposide, and cytarabine (S-MEC). The primary objective was attainment of a complete remission (CR). A Simon two-stage design was used for each of the three arms. The median age of the patients in the FLAM arm was older at 62 years compared with 55 years for the CT arm and the S-MEC arm. The overall response was 14{\%} in the CT arm (5/35, 90{\%} CI 7{\%}-35{\%}), 28{\%} in the FLAM arm (10/36, 90{\%} CI, 16{\%}-43{\%}), and 16{\%} in the S-MEC arm (3/19, 90{\%} CI, 4{\%}-36{\%}). There were nine treatment-related deaths, seven of which occurred in the FLAM arm with four of these in elderly patients. We conclude that the FLAM regimen had an encouraging response rate and should be considered for further clinical development but should be used with caution in elderly patients.",
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Litzow, MR, Wang, XV, Carroll, MP, Karp, JE, Ketterling, RP, Zhang, Y, Kaufmann, SH, Lazarus, HM, Luger, SM, Paietta, EM, Pratz, KW, Tun, HW, Altman, JK, Broun, ER, Rybka, WB, Rowe, JM & Tallman, MS 2019, 'A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease' American Journal of Hematology, vol. 94, no. 1, pp. 111-117. https://doi.org/10.1002/ajh.25333

A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease. / Litzow, Mark R.; Wang, Xin V.; Carroll, Martin P.; Karp, Judith E.; Ketterling, Rhett P.; Zhang, Yanming; Kaufmann, Scott H.; Lazarus, Hillard M.; Luger, Selina M.; Paietta, Elisabeth M.; Pratz, Keith W.; Tun, Han Win; Altman, Jessica K; Broun, Edward R.; Rybka, Witold B.; Rowe, Jacob M.; Tallman, Martin S.

In: American Journal of Hematology, Vol. 94, No. 1, 01.01.2019, p. 111-117.

Research output: Contribution to journalArticle

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T1 - A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease

AU - Litzow, Mark R.

AU - Wang, Xin V.

AU - Carroll, Martin P.

AU - Karp, Judith E.

AU - Ketterling, Rhett P.

AU - Zhang, Yanming

AU - Kaufmann, Scott H.

AU - Lazarus, Hillard M.

AU - Luger, Selina M.

AU - Paietta, Elisabeth M.

AU - Pratz, Keith W.

AU - Tun, Han Win

AU - Altman, Jessica K

AU - Broun, Edward R.

AU - Rybka, Witold B.

AU - Rowe, Jacob M.

AU - Tallman, Martin S.

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N2 - To improve the outcome of relapsed/refractory acute myeloid leukemia (AML), a randomized phase II trial of three novel regimens was conducted. Ninety patients were enrolled and were in first relapse or were refractory to induction/re-induction chemotherapy. They were randomized to the following regimens: carboplatin-topotecan (CT), each by continuous infusion for 5 days; alvocidib (formerly flavopiridol), cytarabine, and mitoxantrone (FLAM) in a timed sequential regimen; or sirolimus combined with mitoxantrone, etoposide, and cytarabine (S-MEC). The primary objective was attainment of a complete remission (CR). A Simon two-stage design was used for each of the three arms. The median age of the patients in the FLAM arm was older at 62 years compared with 55 years for the CT arm and the S-MEC arm. The overall response was 14% in the CT arm (5/35, 90% CI 7%-35%), 28% in the FLAM arm (10/36, 90% CI, 16%-43%), and 16% in the S-MEC arm (3/19, 90% CI, 4%-36%). There were nine treatment-related deaths, seven of which occurred in the FLAM arm with four of these in elderly patients. We conclude that the FLAM regimen had an encouraging response rate and should be considered for further clinical development but should be used with caution in elderly patients.

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