Difference between revisions of "Staging page"

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<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
 
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[[#top|Back to Top]]
 
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</div>
 
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{{#lst:Section editor transclusions|peds}}
 
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<big>''This page contains studies that were specific to pediatric populations. For the more general AML page, follow [[Acute myeloid leukemia|this link]].</big>
 
−
{| class="wikitable" style="float:right; margin-right: 5px;"
 
−
|-
 
−
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
−
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
−
|}
 
−
The following study protocols are included on this page:
 
−
{| class="wikitable sortable" style="width: 50%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |Years of enrollment
 
−
|-
 
−
|UK MRC AML10
 
−
|1988-1995
 
−
|-
 
−
|EORTC 58921
 
−
|1992-2002
 
−
|-
 
−
|I-BFM-SG 2001/01
 
−
|2001-2009
 
−
|-
 
−
|UK MRC AML15
 
−
|2002-2006
 
−
|-
 
−
|St. Jude AML02
 
−
|2002-2008
 
−
|-
 
−
|COG AAML0531
 
−
|2006-2010
 
−
|-
 
−
|St. Jude AML08
 
−
|2008-2017
 
−
|-
 
−
|COG AAML1031
 
−
|2011-2016
 
−
|-
 
−
|COG AAML1421
 
−
|2016-2018
 
−
|-
 
−
|}
 
−
{{TOC limit|limit=4}}
 
−
=Guidelines=
 
−
=="How I Treat"==
 
−
*'''2021:''' Rubnitz & Kaspers [https://doi.org/10.1182/blood.2021011694 How I treat pediatric acute myeloid leukemia]
 
−
=Upfront induction therapy=
 
−
==COG AAML1031 arm A (low-risk)==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part I===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Daunorubicin (Cerubidine)]] 1.7 mg/kg IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
−
**
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''10-day course, followed by:'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part II===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 8
 
−
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 8
 
−
*[[Daunorubicin (Cerubidine)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
**BSA < 0.6 m<sup>2</sup>: 1.7 mg/kg IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).
 
−
**
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''8-day course, followed by:'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part I===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5
 
−
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 through 5
 
−
**BSA < 0.6 m<sup>2</sup>: 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''5-day course, followed by:'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part II===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4
 
−
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
 
−
*[[Mitoxantrone (Novantrone)]] by the following BSA-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 12 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 3 to 6
 
−
**BSA < 0.6 m<sup>2</sup>: 0.4 mg/kg once per day on days 3 to 6
 
−
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Intensification I
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''6-day course'''
 
−
</div></div>
 
−
===References===
 
−
# '''COG AAML1031:''' Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
 
  
−
==COG AAML1031 arm A (high-risk)==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part I===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Daunorubicin (Cerubidine)]] 1.7 mg/kg IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''10-day course, followed by:'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part II===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
 
−
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 3 to 6
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6.
 
−
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction I
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''6-day course, followed by:'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part I===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''5-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part II===
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 2, 8, 9
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 100 mg/kg IV over 3 hours every 12 hours on days 1, 2, 8, 9
 
−
*[[E.Coli L-Asparaginase (LASP)]] 6000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[E.Coli L-Asparaginase (LASP)]] 200 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
may substitute with another asparaginase formulation
 
−
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 25,000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 830 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
If Erwinia asparaginase is not available, pegasparaginase should NOT be given, and asparaginase should be omitted
 
−
'''28-day course'''
 
−
</div></div>
 
−
===References===
 
−
# '''COG AAML1031:''' Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
 
−
 
−
==COG AAML1031 arm C (FLT3/ITD+)==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part I===
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*FLT3/ITD+
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Daunorubicin (Cerubidine)]] 1.7 mg/kg IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 11 to 28
 
−
**see [[Sorafenib Dosing Nomogram]] for more details.
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
−
**
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''28-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part II===
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 1 to 30 minutes every 12 hours on days 1 to 8
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 1 to 30 minutes every 12 hours on days 1 to 8
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Daunorubicin (Cerubidine)]] 1.7 mg/kg IV over 1 to 15 minutes once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 9 to 36
 
−
**see [[Sorafenib Dosing Nomogram]] for more details.
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments).
 
−
**
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''36-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part I===
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 5 mg/kg IV over 60 to 120 minutes once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 6 through 33
 
−
**see [[Sorafenib Dosing Nomogram]] for more details.
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Induction II.
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''33-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part II===
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 1 to 3 hours every 12 hours on days 1 to 4
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 33 mg/kg IV over 1 to 3 hours every 12 hours on days 1 to 4
 
−
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 3 to 6
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Mitoxantrone (Novantrone)]] 0.4 mg/kg once per day on days 3 to 6
 
−
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 200 mg/m<sup>2</sup> (Maximum dose of 400 mg) PO once per day, rounded to accommodate tablet size on days 7 to 34
 
−
**see [[Sorafenib Dosing Nomogram]] for more details
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with the bone marrow evaluation at the end of Intensification I
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''6-day course'''
 
−
</div></div>
 
−
===References===
 
−
# '''COG AAML1031:''' Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S, Levine J, Loken M, Brodersen L, Pollard J, Raimondi S, Kolb EA, Gamis A. Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group. Haematologica. 2020 Jul;105(7):1879-1886. Epub 2020 Feb 6. [https://doi.org/10.3324/haematol.2019.220962 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7327649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32029509/ PubMed] NCT01371981
 
−
==COG AAML0531 arm B (Gemtuzumab)==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part I===
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 15 minutes every 12 hours on days 1 to 10
 
−
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 50 mg/m<sup>2</sup> IV over 6 hours once per day on days 1, 3, 5
 
−
**BSA < 0.6 m<sup>2</sup>: 1.67 mg/kg IV over 6 hours once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 100 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5
 
−
**BSA < 0.6 m<sup>2</sup>: 3.3 mg/kg IV over 4 hours once per day on days 1 to 5
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 3 mg/m<sup>2</sup> IV over 2 hours once on day 6
 
−
**BSA < 0.6 m<sup>2</sup>: 0.1 mg/kg IV once on day 6
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1
 
−
**For CNS positive patients: administer IT cytarabine twice weekly until CSF is clear (Minimum of 4 intrathecal treatments and maximum of 6 intrathecal treatments)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''10-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, part II===
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 15 minutes every 12 hours on days 1 to 8
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Cytarabine (Ara-C)]] 3.3 mg/kg IV over 15 minutes every 12 hours on days 1 to 8
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 6 hours once per day on days 1, 3, 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Daunorubicin (Cerubidine)]] 1.67 mg/kg IV over 6 hours once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5
 
−
**IF BSA < 0.6 m<sup>2</sup>, [[Etoposide (Vepesid)]] 3.3 mg/kg IV over 4 hours once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction I
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''28-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part I===
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 hour every 12 hours on days 1 to 5
 
−
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 hour every 12 hours on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 150 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 5
 
−
**BSA < 0.6 m<sup>2</sup>: 5 mg/kg IV over 4 hours once per day on days 1 to 5
 
−
**Each dose of [[Etoposide (Vepesid)]] should immediately follow the AM dose of [[Cytarabine (Ara-C)]]
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Induction II
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''5-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part II===
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 1000 mg/m<sup>2</sup> IV over 1 hour every 12 hours on days 1 to 4
 
−
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 hour every 12 hours on days 1 to 4
 
−
*[[Mitoxantrone (Novantrone)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 12 mg/m<sup>2</sup> IV over 1 hour once per day on days 3 to 6
 
−
**BSA < 0.6 m<sup>2</sup>: 0.4 mg/kg once per day on days 3 to 6
 
−
**On days where both are given, give [[Mitoxantrone (Novantrone)]] 8 hours AFTER the END of the high dose [[Cytarabine (Ara-C)]] infusions
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 3 mg/m<sup>2</sup> IV over 2 hours once on day 7
 
−
**BSA < 0.6 m<sup>2</sup>: 0.1 mg/kg once on day 7
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT on day 1 or with bone marrow evaluation at the end of Intensification I
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|0 - 0.99
 
−
|20
 
−
|-
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''7-day course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Intensification, part III===
 
−
====Chemotherapy====
 
−
*High Dose [[Cytarabine (Ara-C)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 2, 8, 9
 
−
**BSA < 0.6 m<sup>2</sup>: 33 mg/kg IV over 1 hour every 12 hours on days 1, 2, 8, 9
 
−
*[[E.Coli L-Asparaginase (LASP)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 6000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
**BSA < 0.6 m<sup>2</sup>: 200 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
may substitute with another asparaginase formulation
 
−
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] by the following weight-based criteria:
 
−
**BSA 0.6 m<sup>2</sup> or more: 25,000 IU/m<sup>2</sup> IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
**BSA < 0.6 m<sup>2</sup>: 830 IU/kg IM on Day 2 (at hour 42), Day 9 (at hour 42 after the start of the 1st dose of cytarabine on Day 8)
 
−
'''28-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''COG AAML0531:''' Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
−
==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}==
 
−
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
−
<br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
−
<br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
−
<br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/89/7/2311.long Hann et al. 1997 (UK MRC AML10)]
 
−
|1988-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Acute_myeloid_leukemia_-_historical#DAT|DAT 3+8]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ Gamis et al. 2014 (COG AAML0531)]
 
−
|2006-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: these trials have complicated treatment schemas; see papers for details. This is IND2 for COG AAML0531.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction
 
−
*COG AAML0531: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction versus [[#ADE_.26_GO|ADE & GO]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 8
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*UK MRC AML10: [[#MACE_88|MACE]] consolidation
 
−
*COG AAML0531: [[#CYVE|CYVE]] interim maintenance
 
−
*Other trials: Consolidation (see paper for details)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/89/7/2311.long Hann et al. 1997 (UK MRC AML10)]
 
−
|1988-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Acute_myeloid_leukemia_-_historical#DAT|DAT 3+10]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3171799/ Rubnitz et al. 2010 (AML02)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADE_.28high-dose_Ara-C.29|ADE]]; high-dose Ara-C
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of MRD-positivity at day 22
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ Gamis et al. 2014 (COG AAML0531)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ADE_.26_GO|ADE & GO]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
−
|-
 
−
|}
 
−
''Note: these trials have complicated treatment schemas; see papers for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 or days 2, 4, 6
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5 or days 2 to 6
 
−
'''10-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML10:''' Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed]
 
−
##'''Update:''' Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, Wheatley K; UK Medical Research Council Adult and Children's Leukaemia Working Parties. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet. 1998 Mar 7;351(9104):700-8. [https://doi.org/10.1016/S0140-6736(97)09214-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9504514 PubMed]
 
−
#'''AML02:''' Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010 Jun;11(6):543-52. Epub 2010 May 5. [https://doi.org/10.1016/s1470-2045(10)70090-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3171799/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20451454/ PubMed] NCT00136084
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
#'''COG AAML0531:''' Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
−
==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}==
 
−
ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 
−
<br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 
−
<br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:386dha|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.00327 Rubnitz et al. 2019 (AML08)]
 
−
|2008-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Clofarabine_.26_Cytarabine_99|Clofarabine & Cytarabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior MRD at day 22
 
−
|-
 
−
|}
 
−
''Note: this regimen was intended for patients younger than 22 years.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 2, 4, 6
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
−
'''6-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Response- and risk-adapted therapy; see paper for details
 
−
</div></div>
 
−
===References===
 
−
#'''AML08:''' Rubnitz JE, Lacayo NJ, Inaba H, Heym K, Ribeiro RC, Taub J, McNeer J, Degar B, Schiff D, Yeoh AE, Coustan-Smith E, Wang L, Triplett B, Raimondi SC, Klco J, Choi J, Pounds S, Pui CH. Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial. J Clin Oncol. 2019 Aug 10;37(23):2072-2081. Epub 2019 Jun 27. [https://doi.org/10.1200/jco.19.00327 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7001777/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31246522 PubMed] NCT00703820
 
−
==ADE & GO {{#subobject:e33id7|Regimen=1}}==
 
−
ADE & GO: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposidem, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:99ye46|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ Gamis et al. 2014 (COG AAML0531)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]]
 
−
| style="background-color:#91cf60" |Seems to have superior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV over 2 hours once on day 6
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction
 
−
</div></div>
 
−
===References===
 
−
#'''COG AAML0531:''' Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25092781 PubMed] NCT00372593
 
−
==AIE {{#subobject:948b49|Regimen=1}}==
 
−
AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide
 
−
<br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c7b35a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.nature.com/articles/2403932 Entz-Werle et al. 2005 (EORTC 58921)]
 
−
|1992-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MEC_99|MEC]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
'''7-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''EORTC 58921:''' Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y, Margueritte G, Plouvier E, Boutard P, Vandecruys E, Ferster A, Lutz P, Uyttebroeck A, Hoyoux C, Thyss A, Rialland X, Norton L, Pages MP, Philippe N, Otten J, Behar C; [[Study_Groups#EORTC|EORTC]] Children Leukemia Group. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia. 2005 Dec;19(12):2072-81. [https://www.nature.com/articles/2403932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16136166 PubMed] NCT00002517
 
−
==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}==
 
−
DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|}
 
−
''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|7+3d (standard-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. Both trials have complicated treatment schemas; see papers for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See papers for details (to be completed).
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}==
 
−
DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6a938e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|[[Complex_multipart_regimens#UK_MRC_AML15|See link]]
 
−
|-
 
−
|}
 
−
''This trial has complicated treatment schemas; see papers for details.''
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 
−
'''10-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details (to be completed).
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
==FLAG-Ida {{#subobject:7fc219|Regimen=1}}==
 
−
FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:44e85e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ADE_.28standard-dose_Ara-C.29|ADE 10+3+5]]<br>2. [[#DA_3_.2B_10|DA 3+10]]<br> 3. [[#DA_3_.2B_10.2C_GO|DA 3+10 & GO]]<br> 4. [[#FLAG-Ida_.26_GO_99|FLAG-Ida & GO]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, '''given 4 hours after fludarabine'''
 
−
*[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6
 
−
====Growth factor therapy====
 
−
*[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 
−
##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 
−
=Consolidation after upfront therapy=
 
−
==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}==
 
−
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5d4efb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199605303342203 Ravindranath et al. 1996]
 
−
|1988-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|Intensive chemotherapy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS24
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#7.2B3d_.28standard-dose.29|7+3d]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]]
 
−
{{#lst:Autologous HSCT|5d4efb}}
 
−
</div></div>
 
−
===References===
 
−
#Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. [https://doi.org/10.1056/NEJM199605303342203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8618581 PubMed]
 
−
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}==
 
−
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6ca28d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198712243172602 Brochstein et al. 1987]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|6ca28d}}
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. [https://doi.org/10.1056/NEJM198712243172602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3317056 PubMed]
 
−
=Relapsed or refractory, salvage therapy=
 
−
''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.''
 
−
==COGAAML1421 protocol==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol===
 
−
====Chemotherapy, cycle 1====
 
−
*[[Cytarabine and Daunorubicin Liposome (CPX-351)]] 135 units/m<sup>2</sup> IV over 90 minutes on days 1, 3, 5
 
−
====CNS therapy====
 
−
*[[Cytarabine (Ara-C)]] IT 2 doses
 
−
**At the time of diagnostic lumbar puncture or Day 0 of cycle 1
 
−
**At the time of the Day 28 to 30 bone marrow biopsy, or up to one week prior to Day 1 of cycle 2
 
−
*CNS2 Patients
 
−
**[[Cytarabine (Ara-C)]] IT twice weekly until the CSF is clear starting at least 48 hours following the 3rd dose of CPX-351
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|1 - 1.99
 
−
|30
 
−
|-
 
−
|2 - 2.99
 
−
|50
 
−
|-
 
−
|≥ 3
 
−
|70
 
−
|}
 
−
'''28-Day course'''
 
−
====Chemotherapy, cycle 2====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SQ once per day on days 1 to 5, one hour prior to each dose of [[Fludarabine (Fludara)]]
 
−
**Restart on day 15 and continue until post-nadir ANC ≥ 500/μL
 
−
Pegfilgrastim cannot be utilized in the place of filgrastim or biosimilar
 
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
 
−
*High Dose [[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 1 to 3 hours every once daily on days 1 to 5
 
−
**Begin [[Cytarabine (Ara-C)]] 4 hours after the start of [[Fludarabine (Fludara)]]
 
−
'''28-day course'''
 
−
</div></div>
 
−
===References===
 
−
# '''COG AAML1421:'''Cooper TM, Absalon M, Alonzo TA, Gerbing RB, Leger KJ, Hirsch BA, Pollard JA, Razzouk BI, Aplenc R, Kolb EA. AAML1421, a phase I/II study of CPX-351 followed by fludarabine, cytarabine, and G-CSF (FLAG) for children with relapsed acute myeloid leukemia (AML): A report from the Children's Oncology Group. Journal of Clinical Oncology. 2019 May;37(15). [https://doi.org/10.1200/JCO.2019.37.15_suppl.10003 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32401633/ PubMed]NCT02642965
 
−
==FLAG {{#subobject:551761|Regimen=1}}==
 
−
FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bdc7e4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
 
−
|2001-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR rate
 
−
|-
 
−
|}
 
−
''Note: this regimen was studied in patients up to 21 years of age.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given third, 4 hours after the start of fludarabine'''
 
−
====Growth factor therapy====
 
−
*[[Filgrastim (Neupogen)]] 200 mcg/m<sup>2</sup> (route not specified) once per day on days 0 to 5, '''given first'''
 
−
'''2 cycles (length not specified)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[Regimen_classes#Allogeneic_HSCT|allogeneic HSCT]]
 
−
</div></div>
 
−
===References===
 
−
#'''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
−
=Consolidation after salvage therapy=
 
−
==Cytarabine & Thioguanine {{#subobject:3c38bc|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f2728e|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: this regimen was studied in patients up to 21 years of age, and was intended for use when the time to transplant would be relatively short or for patients in "poor condition".''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 4
 
−
*[[Thioguanine (Tabloid)]] as follows:
 
−
**Cycles 1 & 2: 100 mg/m<sup>2</sup> PO once per day
 
−
'''14-day cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic HSCT]]
 
−
</div></div>
 
−
===References===
 
−
#'''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
−
==CYVE {{#subobject:4bd791|Regimen=1}}==
 
−
CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a16529|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#FLAG|FLAG]] versus [[Acute_myeloid_leukemia_-_historical#FLAG-DNX|FLAG-DNX]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 2000 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV twice per day on days 1 to 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic HSCT]]
 
−
</div></div>
 
−
===References===
 
−
#'''I-BFM-SG 2001/01:''' Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [https://doi.org/10.1200/JCO.2012.43.7384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23319696 PubMed] NCT00186966
 
−
[[Category:Acute myeloid leukemia regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Acute leukemias]]
 
−
[[Category:Pediatric hematologic neoplasms]]
 

Latest revision as of 00:13, 18 June 2023

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