Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia

BDS, JEK

Research output: Contribution to journalArticle

Abstract

Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m2 days 1-3, cytarabine 667 mg/m2/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 mg/m2 day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011- July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m2/day continuous infusion days 1-7 and daunorubicin 90 mg/m2 days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m2/day continuous infusion days 1-5 and daunorubicin 45 mg/m2 days 1- 2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development.

Original languageEnglish (US)
Pages (from-to)1172-1179
Number of pages8
JournalHaematologica
Volume100
Issue number9
DOIs
StatePublished - Sep 7 2015

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alvocidib
Mitoxantrone
Daunorubicin
Cytarabine
Acute Myeloid Leukemia
Disease-Free Survival
Survival
Cytogenetics
Leukemia
Bone Marrow
Safety

ASJC Scopus subject areas

  • Hematology

Cite this

@article{e57b4252fb164428b2a8a781b404c0b8,
title = "Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia",
abstract = "Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m2 days 1-3, cytarabine 667 mg/m2/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 mg/m2 day 9] yields complete remission rates of nearly 70{\%} in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011- July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m2/day continuous infusion days 1-7 and daunorubicin 90 mg/m2 days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m2/day continuous infusion days 1-5 and daunorubicin 45 mg/m2 days 1- 2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70{\%} vs. 46{\%}; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70{\%} vs. 57{\%}; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development.",
author = "BDS and JEK and Zeidner, {Joshua F.} and Foster, {Matthew C.} and Blackford, {Amanda L.} and Litzow, {Mark R.} and Morris, {Lawrence E.} and Strickland, {Stephen A.} and Lancet, {Jeffrey E.} and Prithviraj Bose and {Yair Levy}, M. and Raoul Tibes and Ivana Gojo and Christopher Gocke and Gary Rosner and Little, {Richard F.} and Wright, {John J.} and {Austin Doyle}, L. and Smith, {B Douglas} and Judith Karp",
year = "2015",
month = "9",
day = "7",
doi = "10.3324/haematol.2015.125849",
language = "English (US)",
volume = "100",
pages = "1172--1179",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
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TY - JOUR

T1 - Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia

AU - BDS

AU - JEK

AU - Zeidner, Joshua F.

AU - Foster, Matthew C.

AU - Blackford, Amanda L.

AU - Litzow, Mark R.

AU - Morris, Lawrence E.

AU - Strickland, Stephen A.

AU - Lancet, Jeffrey E.

AU - Bose, Prithviraj

AU - Yair Levy, M.

AU - Tibes, Raoul

AU - Gojo, Ivana

AU - Gocke, Christopher

AU - Rosner, Gary

AU - Little, Richard F.

AU - Wright, John J.

AU - Austin Doyle, L.

AU - Smith, B Douglas

AU - Karp, Judith

PY - 2015/9/7

Y1 - 2015/9/7

N2 - Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m2 days 1-3, cytarabine 667 mg/m2/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 mg/m2 day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011- July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m2/day continuous infusion days 1-7 and daunorubicin 90 mg/m2 days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m2/day continuous infusion days 1-5 and daunorubicin 45 mg/m2 days 1- 2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development.

AB - Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m2 days 1-3, cytarabine 667 mg/m2/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 mg/m2 day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011- July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m2/day continuous infusion days 1-7 and daunorubicin 90 mg/m2 days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m2/day continuous infusion days 1-5 and daunorubicin 45 mg/m2 days 1- 2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development.

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DO - 10.3324/haematol.2015.125849

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VL - 100

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EP - 1179

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JF - Haematologica

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