Acute myeloid leukemia, FLT3-positive

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Note: these are regimens tested in biomarker-specific populations for patients with FLT3 internal tandem duplicated (FLT3-ITD) or tyrosine kinase domain mutated (FLT3-TKD) AML, please see the main AML page for other regimens.
For placebo or observational studies in this condition, please visit this page.
Last updated on 2024-09-06:22 regimens on this page
29 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Acute Myeloid Leukemia.
=Upfront induction therapy, standard patients=
==7+3d (intermediate-dose)==
7+3d: 7 days of cytarabine + 3 days of daunorubicin
===Regimen variant #1===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Phase 3 (C)	1a. 7+3d & Quizartinib1b. 7+3i & Quizartinib	Seems to have shorter OSMedian OS: 15.1 vs 31.9 mo(HR 1.28, 95% CI 1.02-1.61)
Note: this was the lower bound of cytarabine dosing in QuANTUM-First.
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
*Daunorubicin (Cerubidine) 60 mg/m2 IV over 5 minutes once per day on days 1 to 3
7-day course
===Regimen variant #2===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Stone et al. 2017 (RATIFY) 	2008-2011 	Phase 3 (C)	7+3d & Midostaurin 	Seems to have shorter OSMedian OS: 25.6 vs 74.7 mo(HR 1.28, 95% CI 1.04-1.59)
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Phase 3 (C)	1a. 7+3d & Quizartinib1b. 7+3i & Quizartinib	Seems to have shorter OSMedian OS: 15.1 vs 31.9 mo(HR 1.28, 95% CI 1.02-1.61)
Note: this was the upper bound of cytarabine dosing in QuANTUM-First.
====Chemotherapy====
*Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
*Daunorubicin (Cerubidine) 60 mg/m2 IV over 5 minutes once per day on days 1 to 3
====Supportive therapy====
*"According to commonly accepted guidelines with no prophylactic IV antibiotics"
*Granulocyte colony-stimulating factor recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
7-day course
===References===
#RATIFY: Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00651261
#QuANTUM-First: Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02668653
#Q-SOC: NCT04676243
==7+3d & Midostaurin==
7+3d & Midostaurin: 7 days of cytarabine, 3 days of daunorubicin, Midostaurin
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Stone et al. 2017 (RATIFY)	2008-2011 	Phase 3 (E-RT-esc)	7+3d (intermediate-dose)	Seems to have longer OS (primary endpoint)Median OS: 74.7 vs 25.6 mo(HR 0.78, 95% CI 0.63-0.96)
====Chemotherapy====
*Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
*Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Midostaurin (Rydapt) 50 mg PO twice per day on days 8 to 21
====Supportive therapy====
*Hydroxyurea (Hydrea) (no dosage specified) was allowed to be used for up to 5 days before the start of therapy while waiting for results of FLT3 mutation testing
21-day course; retreatment with a second course was allowed if day 21 bone marrow biopsy showed residual AML.
====Subsequent treatment====
*RATIFY, patients who achieved complete remission (CR): HiDAC & Midostaurin consolidation. Stem cell transplantation was allowed.
===References===
#RATIFY: Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00651261
==7+3d & Quizartinib==
7+3d & Quizartinib: 7 days of cytarabine, 3 days of daunorubicin, Quizartinib
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Phase 3 (E-RT-esc)	1a. 7+3d; intermediate-dose1b. 7+3i	Seems to have longer OS (primary endpoint)Median OS: 31.9 vs 15.1 mo(HR 0.78, 95% CI 0.62-0.98)
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day or 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m2)
*Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Quizartinib (Vanflyta) 40 mg PO once per day on days 8 to 21
21-day course; retreatment with a second course was allowed if day 21 bone marrow biopsy showed residual AML.
====Subsequent treatment====
*QuANTUM-First, patients who achieved complete remission (CR): HiDAC & Quizartinib consolidation. Stem cell transplantation was allowed.
===References===
#QuANTUM-First: Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02668653
==7+3i==
7+3i: 7 days of cytarabine + 3 days of idarubicin
===Regimen variant #1===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Phase 3 (C)	1a. 7+3d & Quizartinib1b. 7+3i & Quizartinib	Seems to have shorter OSMedian OS: 15.1 vs 31.9 mo(HR 1.28, 95% CI 1.02-1.61)
Note: this was the lower bound of cytarabine dosing in QuANTUM-First.
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
*Idarubicin 12 mg/m2 IV once per day on days 1 to 3
7-day course
===Regimen variant #2===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Phase 3 (C)	1a. 7+3d & Quizartinib1b. 7+3i & Quizartinib	Seems to have shorter OSMedian OS: 15.1 vs 31.9 mo(HR 1.28, 95% CI 1.02-1.61)
Note: this was the upper bound of cytarabine dosing in QuANTUM-First.
====Chemotherapy====
*Cytarabine (Ara-C) 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m2)
*Idarubicin 12 mg/m2 IV once per day on days 1 to 3
7-day course
===References===
#QuANTUM-First: Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02668653
==7+3i & Quizartinib==
7+3i & Quizartinib: 7 days of cytarabine, 3 days of idarubicin, Quizartinib
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Phase 3 (E-RT-esc)	1a. 7+3d; intermediate-dose1b. 7+3i	Seems to have longer OS (primary endpoint)Median OS: 31.9 vs 15.1 mo(HR 0.78, 95% CI 0.62-0.98)
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day or 200 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m2)
*Idarubicin 12 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Quizartinib (Vanflyta) 40 mg PO once per day on days 8 to 21
21-day course; retreatment with a second course was allowed if day 21 bone marrow biopsy showed residual AML.
====Subsequent treatment====
*QuANTUM-First, patients who achieved complete remission (CR): HiDAC & Quizartinib consolidation. Stem cell transplantation was allowed.
===References===
#QuANTUM-First: Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02668653
==DA 3+10==
DA 3+10: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Burnett et al. 2015 (UK NCRI AML17)	2009-2014 	Phase 3 (C)	DA 3+10; high-dose	Did not meet primary endpoint of OS
Note: this regimen is very similar to 7+3d (intermediate-dose); however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 1 to 10
*Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1, 3, 5
10-day course
====Subsequent treatment====
*DA 3+8 versus DA 3+8 & Lestaurtinib re-induction
===References===
#UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC ISRCTN55675535
##Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article EuroPMC
=First-line induction therapy, older patients or "unfit" patients=
==Azacitidine monotherapy==
===Regimen variant #1, uninterrupted===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wang et al. 2022 (LACEWING)	2016 to not reported	Phase 3 (C)	Azacitidine & Gilteritinib	Did not meet primary endpoint of OSMedian OS: 8.87 vs 9.82 mo(HR 1.09, 95% CI 0.63-1.89)
====Chemotherapy====
*Azacitidine (Vidaza) 75 mg/m2 SC once per day on days 1 to 7
28-day cycles
===Regimen variant #2, interrupted===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wang et al. 2022 (LACEWING)	2016 to not reported	Phase 3 (C)	Azacitidine & Gilteritinib	Did not meet primary endpoint of OSMedian OS: 8.87 vs 9.82 mo(HR 1.09, 95% CI 0.63-1.89)
====Chemotherapy====
*Azacitidine (Vidaza) 75 mg/m2 SC once per day on days 1 to 5, 8, 9
28-day cycles
===References===
#LACEWING: Wang ES, Montesinos P, Minden MD, Lee JH, Heuser M, Naoe T, Chou WC, Laribi K, Esteve J, Altman JK, Havelange V, Watson AM, Gambacorti-Passerini C, Patkowska E, Liu S, Wu R, Philipose N, Hill JE, Gill SC, Rich ES, Tiu RV. Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy. Blood. 2022 Oct 27;140(17):1845-1857. Epub 2022 Aug 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02752035
==7+3d & Sorafenib==
===Regimen===
Study 	Dates of enrollment 	Evidence
Uy et al. 2017 (CALGB 11001)	2011 to not reported	Phase 2
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m2)
*Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 7
7-day course
====Subsequent treatment====
*CALGB 11001, patients not achieving a hypoplastic marrow on day 14: 5+2d & sorafenib re-induction
*CALGB 11001, patients achieving a CR or CRi: IDAC & sorafenib consolidation
===References===
#CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01253070
=Consolidation after upfront therapy=
==HiDAC & Midostaurin==
HiDAC & Midostaurin: High Dose Ara-C (Cytarabine) & Midostaurin
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Stone et al. 2017 (RATIFY)	2008-2011 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*7+3d & midostaurin induction, with CR
====Chemotherapy====
*Cytarabine (Ara-C) 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5 (6 doses per cycle)
====Targeted therapy====
*Midostaurin (Rydapt) 50 mg PO twice per day on days 8 to 21
28-day cycle for 4 cycles
====Subsequent treatment====
*Stem cell transplantation "was allowed" for eligible patients; others proceeded to midostaurin maintenance
===References===
#RATIFY: Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00651261
==HiDAC & Quizartinib==
HiDAC & Quizartinib: High Dose Ara-C (Cytarabine) & Quizartinib
===Regimen===
Study 	Dates of enrollment 	Evidence
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Non-randomized part of phase 3 RCT
Note: Patients undergoing allogeneic HSCT after consolidation proceeded to maintenance anytime between day +30 and day +180.
====Preceding treatment====
*7+3d & Quizartinib or 7+3i & Quizartinib induction, with CR
====Chemotherapy====
*Cytarabine (Ara-C) by the following age-based criteria:
**Younger than 60 years old: 3000 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5 (6 doses per cycle)
**60 years old or older: 1500 mg/m2 IV over 3 hours every 12 hours on days 1, 3, 5 (6 doses per cycle)
====Targeted therapy====
*Quizartinib (Vanflyta) 40 mg PO once per day on days 6 to 19
Up to 4 cycles
====Subsequent treatment====
*Quizartinib maintenance (see note)
===References===
#QuANTUM-First: Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02668653
==IDAC & Sorafenib==
IDAC & Sorafenib: Intermediate Dose Ara-C (Cytarabine) & Sorafenib
===Regimen===
Study 	Dates of enrollment 	Evidence
Uy et al. 2017 (CALGB 11001)	2011 to not reported	Phase 2
====Preceding treatment====
*7+3d & sorafenib induction
====Chemotherapy====
*Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours once per day on days 1 to 5
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 28
4- to 6-week cycle for 2 cycles
====Subsequent treatment====
*Sorafenib maintenance
===References===
#CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01253070
=Maintenance after upfront therapy, including allogeneic HSCT=
==Midostaurin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Stone et al. 2017 (RATIFY)	2008-2011 	Non-randomized part of phase 3 RCT	CR rate: 59% after induction
====Preceding treatment====
*HiDAC & Midostaurin consolidation
====Targeted therapy====
*Midostaurin (Rydapt) 50 mg PO twice per day on days 1 to 28
28-day cycle for up to 13 cycles (1 year)
===References===
#RATIFY: Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00651261
#ARO-021: NCT03258931
#HOVON 156 AML: NCT04027309
==Quizartinib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Erba et al. 2023 (QuANTUM-First)	2016-09-27 to 2019-08-14	Non-randomized part of phase 3 RCT
Note: Patients undergoing allogeneic HSCT after consolidation began maintenance anytime between day +30 and day +180. The dose of quizartinib was increased only if the mean QT interval corrected with Fridericia's formula [QTcF] was less than or equal to 450 ms on C1D15.
====Preceding treatment====
*HiDAC & Quizartinib consolidation, +/- allogeneic HSCT
====Targeted therapy====
*Quizartinib (Vanflyta) as follows:
**Cycle 1: 30 mg PO once per day on days 1 to 14, then 60 mg PO once per day on days 15 to 28
**Cycles 2 to 36: 60 mg PO once per day on days 1 to 28
28-day cycle for up to 36 cycles (3 years)
===References===
#QuANTUM-First: Erba HP, Montesinos P, Kim HJ, Patkowska E, Vrhovac R, Žák P, Wang PN, Mitov T, Hanyok J, Kamel YM, Rohrbach JEC, Liu L, Benzohra A, Lesegretain A, Cortes J, Perl AE, Sekeres MA, Dombret H, Amadori S, Wang J, Levis MJ, Schlenk RF; QuANTUM-First Study Group. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 May 13;401(10388):1571-1583. Epub 2023 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02668653
==Sorafenib monotherapy==
===Regimen variant #1, 6 months===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Xuan et al. 2020 (Sorafenib-Flt3 AML-2015)	2015-06-20 to 2018-07-21	Phase 3 (E-esc)	Observation	Higher 1-year cumulative incidence of relapse (primary endpoint)Longer OS1 (secondary endpoint)OS60: 72% vs 55.9%(HR 0.55, 95% CI 0.34-0.88)
1Reported efficacy is based on the 2023 update.
====Preceding treatment====
*Allogeneic stem cell transplant consolidation
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day on days +30 to +180
6-month course
===Regimen variant #2, 12 mos===
Study 	Dates of enrollment 	Evidence
Uy et al. 2017 (CALGB 11001)	2011 to not reported	Phase 2
====Preceding treatment====
*IDAC & Sorafenib consolidation
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 28
28-day cycle for up to 12 cycles
===Regimen variant #3, 2 years===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Burchert et al. 2020 (SORMAIN)	2010-2016 	Phase 3 (E-esc)	Placebo 	Longer RFS (primary endpoint)RFS24: 85% vs 53.3%(HR 0.39, 95% CI 0.18-0.85)
Note: dose was escalated only if tolerated.
====Preceding treatment====
*Allogeneic stem cell transplant consolidation
====Targeted therapy====
*Sorafenib (Nexavar) as follows:
**Cycle 1: 200 mg PO twice per day on days 1 to 14, then 400 mg PO twice per day on days 15 to 28
**Cycles 2 to 26: 400 mg PO twice per day on days 1 to 28
28-day cycle for up to 26 cycles (2 years)
===References===
#CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01253070
#SORMAIN: Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, Wollmer E, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner EM, Kröger N, Wolschke C, Schleuning M, Götze KS, Schmid C, Crysandt M, Eßeling E, Wolf D, Wang Y, Böhm A, Thiede C, Haferlach T, Michel C, Bethge W, Wündisch T, Brandts C, Harnisch S, Wittenberg M, Hoeffkes HG, Rospleszcz S, Burchardt A, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK. Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN). J Clin Oncol. 2020 Sep 10;38(26):2993-3002. Epub 2020 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC Link to clinical trial registration DRKS00000591
#Sorafenib-Flt3 AML-2015: Xuan L, Wang Y, Huang F, Fan Z, Xu Y, Sun J, Xu N, Deng L, Li X, Liang X, Luo X, Shi P, Liu H, Wang Z, Jiang L, Yu C, Zhou X, Lin R, Chen Y, Tu S, Huang X, Liu Q. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1201-1212. Epub 2020 Aug 10. link to original article EuroPMC NCT02474290
##Update: Xuan L, Wang Y, Yang K, Shao R, Huang F, Fan Z, Chi P, Xu Y, Xu N, Deng L, Li X, Liang X, Luo X, Shi P, Liu H, Wang Z, Jiang L, Lin R, Chen Y, Tu S, Zhang Y, Sun J, Huang X, Liu Q. Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Aug;10(8):e600-e611. Epub 2023 Jul 3. link to original article EuroPMC
=Relapsed or refractory, salvage therapy=
==Midostaurin monotherapy==
===Regimen variant #1===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Fischer et al. 2010 (CPKC412A2104)	2002 to not reported	Randomized phase 2b (E-de-esc)	Midostaurin; 100 mg twice per day	Not reported
====Targeted therapy====
*Midostaurin (Rydapt) 50 mg PO twice per day on days 1 to 28
28-day cycles
===Regimen variant #2===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Fischer et al. 2010 (CPKC412A2104)	2002 to not reported	Randomized phase 2b (E-esc)	Midostaurin; 50 mg twice per day	Not reported
====Targeted therapy====
*Midostaurin (Rydapt) 100 mg PO twice per day on days 1 to 28
28-day cycles
===Regimen variant #3===
Study 	Dates of enrollment	Evidence
Stone et al. 2004	Not reported 	Phase 2
====Biomarker eligibility criteria====
*FLT3 ITD or FLT3 p.D835Y mutation
====Targeted therapy====
*Midostaurin (Rydapt) 75 mg PO three times per day on days 1 to 28
28-day cycles
===References===
#Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005 Jan 1;105(1):54-60. Epub 2004 Sep 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#CPKC412A2104: Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ. Phase IIB trial of oral midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. Epub 2010 Aug 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00045942
=Relapsed or refractory, further lines of therapy=
==Azacitidine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Perl et al. 2019 (ADMIRAL)	2015-2018 	Phase 3 (C)	Gilteritinib	Shorter OSMedian OS: 5.6 vs 9.3 mo(HR 1.50, 95% CI 1.18-1.92)
Note: Perl et al. 2019 does not contain dosing information for the control arm regimens; the dosing here is from other AML regimens.
====Chemotherapy====
*Azacitidine (Vidaza) 75 mg/m2 SC once per day on days 1 to 7
28-day cycle for at least 4 cycles
===References===
#ADMIRAL: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-40. link to original article does not contain dosing details EuroPMC NCT02421939
##Update: Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. link to original article link to PMC article EuroPMC
##PRO analysis: Ritchie EK, Cella D, Fabbiano F, Pigneux A, Kanda Y, Ivanescu C, Pandya BJ, Shah MV. Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML. Leuk Lymphoma. 2023 May;64(5):938-950. Epub 2023 Apr 5. link to original article EuroPMC
==Azacitidine & Sorafenib==
===Regimen===
Study 	Dates of enrollment	Evidence
Ravandi et al. 2013 (MDACC 2010-0511)	2011-2012 	Phase 2
====Chemotherapy====
*Azacitidine (Vidaza) 75 mg/m2 IV or SC once per day on days 1 to 7
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day
====Supportive therapy====
*"All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."
4- to 8-week cycles
===References===
#MDACC 2010-0511: Ravandi F, Alattar ML, Grunwald MR, Rudek MA, Rajkhowa T, Richie MA, Pierce S, Daver N, Garcia-Manero G, Faderl S, Nazha A, Konopleva M, Borthakur G, Burger J, Kadia T, Dellasala S, Andreeff M, Cortes J, Kantarjian H, Levis M. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013 Jun 6;121(23):4655-62. Epub 2013 Apr 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01254890
==FLAG-Ida==
FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Filgrastim), Idarubicin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cortes et al. 2019 (QuANTUM-R)	2014-2017 	Phase 3 (C)	Quizartinib 	Seems to have shorter OSMedian OS: 4.7 vs 6.2 mo(HR 1.32, 95% CI 1.02-1.72)
Perl et al. 2019 (ADMIRAL) 	2015-2018 	Phase 3 (C)	Gilteritinib	Shorter OSMedian OS: 5.6 vs 9.3 mo(HR 1.50, 95% CI 1.18-1.92)
====Chemotherapy====
*Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days 2 to 6
*Cytarabine (Ara-C) 2000 mg/m2 IV once per day on days 2 to 6
*Idarubicin (Idamycin) 10 mg/m2 IV once per day on days 2 to 4
====Growth factor therapy====
*Filgrastim (Neupogen) 5 mcg/kg or 300 mcg/m2 SC once per day on days 1 to 5
28-day cycle for up to 2 cycles
===References===
#QuANTUM-R: Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, Krämer A, Dombret H, Hogge D, Jonas BA, Leung AY, Mehta P, Montesinos P, Radsak M, Sica S, Arunachalam M, Holmes M, Kobayashi K, Namuyinga R, Ge N, Yver A, Zhang Y, Levis MJ. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):984-997. Epub 2019 Jun 4. Erratum in: Lancet Oncol. 2019 Jul;20(7):e346. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02039726
#ADMIRAL: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-40. link to original article does not contain dosing details EuroPMC NCT02421939
##Update: Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. link to original article link to PMC article EuroPMC
##PRO analysis: Ritchie EK, Cella D, Fabbiano F, Pigneux A, Kanda Y, Ivanescu C, Pandya BJ, Shah MV. Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML. Leuk Lymphoma. 2023 May;64(5):938-950. Epub 2023 Apr 5. link to original article EuroPMC
#ARO-013: NCT03250338
==Gilteritinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Perl et al. 2017 (2215-CL-0101) 	2013-2015 	Phase 1/2 	 	
Perl et al. 2019 (ADMIRAL) 	2015-2018 	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. MEC1b. FLAG-Ida1c. LoDAC1d. Azacitidine	Longer OS1 (co-primary endpoint)Median OS: 9.3 vs 5.6 mo(HR 0.665, 95% CI 0.52-0.85)
Awaiting publication (2215-CL-0303)	2018-2023 	Phase 3 (E-switch-ooc) 	1a. MEC1b. FLAG1c. LoDAC 	TBD if different primary endpoint of OS
1Reported efficacy is based on the 2022 update.
====Targeted therapy====
*Gilteritinib (Xospata) 120 mg PO once per day on days 1 to 28
28-day cycles
===References===
#2215-CL-0101: Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Röllig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017 Aug;18(8):1061-1075. Epub 2017 Jun 20. link to original article link to PMC article EuroPMC NCT02014558
#ADMIRAL: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-40. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02421939
##Update: Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. link to original article link to PMC article EuroPMC
##PRO analysis: Ritchie EK, Cella D, Fabbiano F, Pigneux A, Kanda Y, Ivanescu C, Pandya BJ, Shah MV. Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML. Leuk Lymphoma. 2023 May;64(5):938-950. Epub 2023 Apr 5. link to original article EuroPMC
#2215-CL-0303: NCT03182244
==Low-dose Cytarabine monotherapy (LoDAC)==
LoDAC: Low Dose Ara-C (cytarabine)
LDAC: Low Dose Ara-C (cytarabine)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cortes et al. 2019 (QuANTUM-R)	2014-2017 	Phase 3 (C)	Quizartinib 	Seems to have shorter OSMedian OS: 4.7 vs 6.2 mo(HR 1.32, 95% CI 1.02-1.72)
Perl et al. 2019 (ADMIRAL) 	2015-2018 	Phase 3 (C)	Gilteritinib	Shorter OSMedian OS: 5.6 vs 9.3 mo(HR 1.50, 95% CI 1.18-1.92)
====Chemotherapy====
*Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10
28-day cycles
===References===
#QuANTUM-R: Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, Krämer A, Dombret H, Hogge D, Jonas BA, Leung AY, Mehta P, Montesinos P, Radsak M, Sica S, Arunachalam M, Holmes M, Kobayashi K, Namuyinga R, Ge N, Yver A, Zhang Y, Levis MJ. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):984-997. Epub 2019 Jun 4. Erratum in: Lancet Oncol. 2019 Jul;20(7):e346. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02039726
#ADMIRAL: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-40. link to original article does not contain dosing details EuroPMC NCT02421939
##Update: Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. link to original article link to PMC article EuroPMC
##PRO analysis: Ritchie EK, Cella D, Fabbiano F, Pigneux A, Kanda Y, Ivanescu C, Pandya BJ, Shah MV. Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML. Leuk Lymphoma. 2023 May;64(5):938-950. Epub 2023 Apr 5. link to original article EuroPMC
==MEC==
MEC: Mitoxantrone, Etoposide, Cytarabine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cortes et al. 2019 (QuANTUM-R)	2014-2017 	Phase 3 (C)	Quizartinib 	Seems to have shorter OSMedian OS: 4.7 vs 6.2 mo(HR 1.32, 95% CI 1.02-1.72)
Perl et al. 2019 (ADMIRAL) 	2015-2018 	Phase 3 (C)	Gilteritinib	Shorter OSMedian OS: 5.6 vs 9.3 mo(HR 1.50, 95% CI 1.18-1.92)
====Chemotherapy====
*Mitoxantrone (Novantrone) 8 mg/m2 IV push once per day on days 1 to 5, given third
*Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 5, given first
*Cytarabine (Ara-C) 1000 mg/m2 IV once per day on days 1 to 5, given second
28-day cycle for 1 to 2 cycles
===References===
#QuANTUM-R: Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, Krämer A, Dombret H, Hogge D, Jonas BA, Leung AY, Mehta P, Montesinos P, Radsak M, Sica S, Arunachalam M, Holmes M, Kobayashi K, Namuyinga R, Ge N, Yver A, Zhang Y, Levis MJ. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):984-997. Epub 2019 Jun 4. Erratum in: Lancet Oncol. 2019 Jul;20(7):e346. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02039726
#ADMIRAL: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-40. link to original article does not contain dosing details EuroPMC NCT02421939
##Update: Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. link to original article link to PMC article EuroPMC
##PRO analysis: Ritchie EK, Cella D, Fabbiano F, Pigneux A, Kanda Y, Ivanescu C, Pandya BJ, Shah MV. Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML. Leuk Lymphoma. 2023 May;64(5):938-950. Epub 2023 Apr 5. link to original article EuroPMC
==Quizartinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cortes et al. 2019 (QuANTUM-R)	2014-2017 	Phase 3 (E-switch-ooc)	Investigator's choice of:1a. LoDAC1b. MEC1c. FLAG-Ida	Seems to have longer OS (primary endpoint)Median OS: 6.2 vs 4.7 mo(HR 0.76, 95% CI 0.58-0.98)
Note: Quizartinib was studied at a variety of doses; references are provided below for historic context; the dose here is from QuANTUM-R, and was only increased if certain QTc parameters were met; see the paper for details.
====Targeted therapy====
*Quizartinib (Vanflyta) as follows:
**Cycle 1: 30 mg PO once per day on days 1 to 15, then 60 mg PO once per day on days 16 to 28
**Cycle 2 onwards: 60 mg PO once per day on days 1 to 28
28-day cycles
===References===
# CP0001: Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. Epub 2013 Sep 3. link to original article link to PMC article EuroPMC NCT00462761
# ACEAML: Cortes J, Perl AE, Döhner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Krämer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. Epub 2018 May 31. link to original article link to PMC article EuroPMC NCT00989261
# 2689-CL-2004: Cortes JE, Tallman MS, Schiller GJ, Trone D, Gammon G, Goldberg SL, Perl AE, Marie JP, Martinelli G, Kantarjian HM, Levis MJ. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML. Blood. 2018 Aug 9;132(6):598-607. Epub 2018 Jun 6. link to original article link to PMC article EuroPMC NCT01565668
#QuANTUM-R: Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, Krämer A, Dombret H, Hogge D, Jonas BA, Leung AY, Mehta P, Montesinos P, Radsak M, Sica S, Arunachalam M, Holmes M, Kobayashi K, Namuyinga R, Ge N, Yver A, Zhang Y, Levis MJ. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):984-997. Epub 2019 Jun 4. Erratum in: Lancet Oncol. 2019 Jul;20(7):e346. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02039726
=Prognosis=
==Prognosis in cytogenetically normal AML==
#Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome: Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. link to original article EuroPMC
Category:Acute myeloid leukemia regimens
Category:Biomarker-specific pages
Category:Acute leukemias