Difference between revisions of "Acute myeloid leukemia, FLT3-positive"

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|}
 
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====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
 
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
 
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
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'''7-day course'''
 
'''7-day course'''
 
====Subsequent treatment====
 
====Subsequent treatment====
 +
 
*Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 & sorafenib
 
*Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 & sorafenib
 
*Patients achieving a CR or CRi: [[#IDAC_.26_Sorafenib|IDAC & sorafenib consolidation]]
 
*Patients achieving a CR or CRi: [[#IDAC_.26_Sorafenib|IDAC & sorafenib consolidation]]
  
 
===References===
 
===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. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed]
+
 
 +
#'''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. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed]
  
 
=Consolidation after upfront therapy=
 
=Consolidation after upfront therapy=
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|}
 
|}
 
====Preceding treatment====
 
====Preceding treatment====
 +
 
*[[#7.2B3d_.26_Sorafenib|7+3d & sorafenib induction]]
 
*[[#7.2B3d_.26_Sorafenib|7+3d & sorafenib induction]]
 +
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5
 
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5
 
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 28
 
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 28
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'''4- to 6-week cycle for 2 cycles'''
 
'''4- to 6-week cycle for 2 cycles'''
 
====Subsequent treatment====
 
====Subsequent treatment====
 +
 
*[[#Sorafenib_monotherapy|Sorafenib maintenance]]
 
*[[#Sorafenib_monotherapy|Sorafenib maintenance]]
  
 
===References===
 
===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. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed]
+
 
 +
#'''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. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed]
  
 
=Maintenance after upfront therapy, including allogeneic HSCT=
 
=Maintenance after upfront therapy, including allogeneic HSCT=
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|}
 
|}
 
====Preceding treatment====
 
====Preceding treatment====
 +
 
*[[#IDAC_.26_Sorafenib|IDAC & Sorafenib consolidation]]
 
*[[#IDAC_.26_Sorafenib|IDAC & Sorafenib consolidation]]
 +
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day  
+
 
 +
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
  
 
'''28-day cycle for up to 12 cycles'''
 
'''28-day cycle for up to 12 cycles'''
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|}
 
|}
 
====Preceding treatment====
 
====Preceding treatment====
 +
 
*Allogeneic stem cell transplant
 
*Allogeneic stem cell transplant
 +
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Sorafenib (Nexavar)]] as follows:
 
*[[Sorafenib (Nexavar)]] as follows:
 
**Cycle 1: 200 mg PO twice per day on days 1 to 14, then increasing to 400 mg PO twice per day if tolerated
 
**Cycle 1: 200 mg PO twice per day on days 1 to 14, then increasing to 400 mg PO twice per day if tolerated
Line 130: Line 144:
  
 
===References===
 
===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. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed]
+
 
−
# '''Abstract:''' Burchert A, Bug G, Finke J, Stelljes M, Rollig C, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner E, Kroeger N, Wolschke C, Schleuning M, Elmaagacli A, Götze KS, Schmid C, Jost E, Wolf D, Böhm A, Thiede C, Haferlach T, Bethge W, Harnisch S, Wittenberg M, Rospleszcz S, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK. Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain Trial. Blood 2018, 132(Suppl 1), 661. Accessed February 13, 2019. [http://www.bloodjournal.org/content/132/Suppl_1/661.abstract link to abstract] '''contains verified protocol''' [https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-018539-16/AT Link to clinical trial registration]
+
#'''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. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed]
 +
#'''Abstract:''' Burchert A, Bug G, Finke J, Stelljes M, Rollig C, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner E, Kroeger N, Wolschke C, Schleuning M, Elmaagacli A, Götze KS, Schmid C, Jost E, Wolf D, Böhm A, Thiede C, Haferlach T, Bethge W, Harnisch S, Wittenberg M, Rospleszcz S, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK. Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain Trial. Blood 2018, 132(Suppl 1), 661. Accessed February 13, 2019. [http://www.bloodjournal.org/content/132/Suppl_1/661.abstract link to abstract] '''contains verified protocol''' [https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-018539-16/AT Link to clinical trial registration]
  
 
=Relapsed or refractory, salvage therapy=
 
=Relapsed or refractory, salvage therapy=
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|}
 
|}
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Midostaurin (Rydapt)]] 50 mg PO twice per day
 
*[[Midostaurin (Rydapt)]] 50 mg PO twice per day
  
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|}
 
|}
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Midostaurin (Rydapt)]] 100 mg PO twice per day
 
*[[Midostaurin (Rydapt)]] 100 mg PO twice per day
  
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''Patients were required to have a FLT3 ITD or FLT3 p.D835Y mutation.''
 
''Patients were required to have a FLT3 ITD or FLT3 p.D835Y mutation.''
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Midostaurin (Rydapt)]] 75 mg PO three times per day
 
*[[Midostaurin (Rydapt)]] 75 mg PO three times per day
  
Line 187: Line 205:
  
 
===References===
 
===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. [http://www.bloodjournal.org/content/105/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15345597 PubMed]
+
 
 +
#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. [http://www.bloodjournal.org/content/105/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15345597 PubMed]
 
<!-- Presented in part at the 45th Annual Meeting of the American Society of Hematology, December 6-9, 2003, San Diego, CA. -->
 
<!-- Presented in part at the 45th Annual Meeting of the American Society of Hematology, December 6-9, 2003, San Diego, CA. -->
−
# 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. [http://jco.ascopubs.org/content/28/28/4339.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135183/ link to PMC article] '''contains verified protocol'''[https://www.ncbi.nlm.nih.gov/pubmed/20733134 PubMed]
+
#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. [http://jco.ascopubs.org/content/28/28/4339.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135183/ link to PMC article] '''contains verified protocol'''[https://www.ncbi.nlm.nih.gov/pubmed/20733134 PubMed]
  
 
=Relapsed or refractory, further lines of therapy=
 
=Relapsed or refractory, further lines of therapy=
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|}
 
|}
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Gilteritinib (Xospata)]] 120 mg PO once per day
 
*[[Gilteritinib (Xospata)]] 120 mg PO once per day
  
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===References===
 
===References===
−
# 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30416-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28645776 PubMed]
+
 
−
# ADMIRAL [https://clinicaltrials.gov/ct2/show/NCT02421939 Clinical Trial]
+
#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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30416-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28645776 PubMed]
 +
#ADMIRAL [https://clinicaltrials.gov/ct2/show/NCT02421939 Clinical Trial]
  
 
==Azacitidine & Sorafenib {{#subobject:e3a8ee|Regimen=1}}==
 
==Azacitidine & Sorafenib {{#subobject:e3a8ee|Regimen=1}}==
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|}
 
|}
 
====Chemotherapy====
 
====Chemotherapy====
 +
 
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 
*[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
 
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
  
 
====Supportive medications====
 
====Supportive medications====
−
* "All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."
+
 
 +
*"All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."
  
 
'''4- to 8-week cycles'''
 
'''4- to 8-week cycles'''
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===References===
 
===References===
 
<!-- no pre-pub disclosed -->
 
<!-- no pre-pub disclosed -->
−
# 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. [http://www.bloodjournal.org/content/121/23/4655.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23613521 PubMed]
 
  
−
= Investigational agents =
+
#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. [http://www.bloodjournal.org/content/121/23/4655.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23613521 PubMed]
 +
#
 +
 
 +
==Quizartinib monotherapy {{#subobject:0384e2|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===Regimen {{#subobject:10f04d|Variant=1}}===
 +
{| class="wikitable" style="width: 100%; text-align:center;"
 +
! style="width: 25%" |Study
 +
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 25%" |Comparator
 +
! style="width: 25%" |[[Levels of Evidence|Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(19)30150-0 Cortes et al 2019 (QuANTUM-R)]
 +
| style="background-color:#1a9851" |Phase III (E)
 +
|Salvage Chemotherapy
 +
|Superior OS
 +
|}
 +
====Chemotherapy====
 +
 
 +
*[[Quizartinib (AC220)|Quizartinib]] 60 mg PO once per day
 +
 
 +
===References===
 +
 
 +
#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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30150-0/fulltext link to original article] [pmid:31175001 PubMed]
 +
 
 +
=Investigational agents=
 
''These are drugs under study with at least some promising results for this disease.''
 
''These are drugs under study with at least some promising results for this disease.''
−
* [[Quizartinib (AC220)]]
+
 
 +
*[[Quizartinib (AC220)]]
 +
 
 
[[Category:Acute myeloid leukemia regimens]]
 
[[Category:Acute myeloid leukemia regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Acute leukemias]]
 
[[Category:Acute leukemias]]

Revision as of 02:19, 11 August 2019

Section editor
MartinSchoen.jpg
 Martin W. Schoen, MD, MPH
Saint Louis University
St. Louis, MO
Social-twitter-icon.pngmwschoen

Note: these are biomarker-specific regimens 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.

22 regimens on this page
26 variants on this page


Upfront induction therapy, standard patients

7+3d & Midostaurin

Cytarabine, Daunorubicin, and Midostaurin induction therapy for acute myeloid leukemia (AML)

First-line induction therapy, older patients or "unfit" patients

7+3d & Sorafenib

back to top

Regimen

Study Evidence
Uy et al. 2017 (CALGB 11001) Phase II

Chemotherapy

7-day course

Subsequent treatment

  • Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 & sorafenib
  • Patients achieving a CR or CRi: IDAC & sorafenib consolidation

References

  1. 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 contains verified protocol link to PMC article PubMed

Consolidation after upfront therapy

HiDAC & Midostaurin

Cytarabine & Midostaurin consolidation therapy for acute myeloid leukemia (AML)

IDAC & Sorafenib

back to top

IDAC & Sorafenib: Intermediate Dose Ara-C (Cytarabine) & Sorafenib

Regimen

Study Evidence
Uy et al. 2017 (CALGB 11001) Phase II

Preceding treatment

Chemotherapy

4- to 6-week cycle for 2 cycles

Subsequent treatment

References

  1. 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 contains verified protocol link to PMC article PubMed

Maintenance after upfront therapy, including allogeneic HSCT

Midostaurin monotherapy

Midostaurin (Rydapt) maintenance therapy for acute myeloid leukemia (AML)

Sorafenib monotherapy

back to top

Variant #1, 12 mos

Study Evidence
Uy et al. 2017 (CALGB 11001) Phase II

Preceding treatment

Chemotherapy

28-day cycle for up to 12 cycles

Variant #2, 2 years

Study Evidence Comparator Efficacy
Burchert et al. 2018 (SORMAIN) Phase III (E) Placebo Seems to have superior RFS

Preceding treatment

  • Allogeneic stem cell transplant

Chemotherapy

  • Sorafenib (Nexavar) as follows:
    • Cycle 1: 200 mg PO twice per day on days 1 to 14, then increasing to 400 mg PO twice per day if tolerated
    • Cycles 2 to 26: 400 mg PO twice per day

28-day cycle for up to 26 cycles (2 years)

References

  1. 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 contains verified protocol link to PMC article PubMed
  2. Abstract: Burchert A, Bug G, Finke J, Stelljes M, Rollig C, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner E, Kroeger N, Wolschke C, Schleuning M, Elmaagacli A, Götze KS, Schmid C, Jost E, Wolf D, Böhm A, Thiede C, Haferlach T, Bethge W, Harnisch S, Wittenberg M, Rospleszcz S, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK. Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain Trial. Blood 2018, 132(Suppl 1), 661. Accessed February 13, 2019. link to abstract contains verified protocol Link to clinical trial registration

Relapsed or refractory, salvage therapy

Midostaurin monotherapy

back to top

Variant #1

Study Evidence Comparator
Fischer et al. 2010 Randomized Phase IIB (E) Midostaurin 100 mg twice per day

Chemotherapy

Continued indefinitely

Variant #2

Study Evidence Comparator
Fischer et al. 2010 Randomized Phase IIB (E) Midostaurin 50 mg twice per day

Chemotherapy

Continued indefinitely

Variant #3

Study Evidence
Stone et al. 2004 Phase II

Patients were required to have a FLT3 ITD or FLT3 p.D835Y mutation.

Chemotherapy

28-day cycles

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocolPubMed

Relapsed or refractory, further lines of therapy

Gilteritinib monotherapy

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Regimen

FDA-recommended dose
Study Evidence Comparator Efficacy
Perl et al. 2017 Phase I/II
ADMIRAL Phase III (E) Salvage Chemotherapy Not reported

Chemotherapy

28-day cycles

References

  1. 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 PubMed
  2. ADMIRAL Clinical Trial

Azacitidine & Sorafenib

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Regimen

Study Evidence
Ravandi et al. 2013 Phase II

Chemotherapy

Supportive medications

  • "All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."

4- to 8-week cycles

References

  1. 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 contains verified protocol link to PMC article PubMed

Quizartinib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Cortes et al 2019 (QuANTUM-R) Phase III (E) Salvage Chemotherapy Superior OS

Chemotherapy

References

  1. 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. link to original article [pmid:31175001 PubMed]

Investigational agents

These are drugs under study with at least some promising results for this disease.

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