Difference between revisions of "Staging page"

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<span id="BackToTop"></span>
 
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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}}
 
−
<big>''This page contains studies that are specific to pediatric populations. For the more general B-cell acute lymphoblastic leukemia page, including regimens for adolescents and young adults, follow [[B-cell acute lymphoblastic 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>
 
−
|}
 
−
{{TOC limit|limit=4}}
 
−
=Guidelines=
 
−
=="How I Treat"==
 
−
*'''2020:''' Hunger & Raetz. [https://doi.org/10.1182/blood.2019004043 How I treat relapsed acute lymphoblastic leukemia in the pediatric population]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia]
 
−
=Upfront therapy=
 
−
==COG AALL0932 protocol for standard-risk==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, Pegaspargase, Vincristine, Dexamethasone {{#subobject:15hgu1|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ Maloney et al. 2019 (COG AALL0331)]
 
−
|2005-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: there are very minor differences in timing between protocols; see papers for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV once over 1 to 2 hours on day 4
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT once on day 0
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Initial Dose
 
−
|-
 
−
|1 - 1.99 years
 
−
|30 mg
 
−
|-
 
−
|2 - 2.99 years
 
−
|50 mg
 
−
|-
 
−
|≥ 3 years
 
−
|70 mg
 
−
|}
 
−
CNS2 Patients will receive an additional dose of [[Cytarabine (Ara-C)]] IT on either day 4, 5, or 6, followed by [[Methotrexate (MTX)]] IT on day 8 and then another dose of [[Cytarabine (Ara-C)]] IT on either day 11 or 12 according to the following dosing.
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Subsequent Doses
 
−
|-
 
−
|1 - 1.99
 
−
|20 mg
 
−
|-
 
−
|2 - 2.99
 
−
|30 mg
 
−
|-
 
−
|≥ 3
 
−
|40 mg
 
−
|}
 
−
*[[Methotrexate (MTX)]] IT once per day on days 8, 29
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
====Supportive therapy, DS Arm====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> PO x 2 doses given 48 and 60 hours after the lumbar puncture on days 10, 11, 31, 32
 
−
'''35-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*COG AALL0331, M2 marrow or M1 marrow with MRD of at least 1% at day 29: Extended induction
 
−
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Consolidation, Mercaptopurine & Vincristine {{#subobject:171gc1|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Pegaspargase.2C_Vincristine.2C_Dexamethasone|Pegaspargase, Vincristine, Dexamethasone]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/day PO on days 1 to 28
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
====Supportive therapy, DS Arm====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> PO x 2 doses given 48 and 60 hours after the lumbar puncture on days 3, 4, 10, 11, 17, 18.
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, I (Methotrexate & Vincristine) {{#subobject:0ae09f|Regimen=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/PMC3138679/ Matloub et al. 2011 (COG CCG-1991)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Mercaptopurine.2C_Methotrexate.2C_Vincristine.2C_Dexamethasone_88|Mercaptopurine, MTX, Vincristine, Dexamethasone]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV once on day 1, then 150 mg/m<sup>2</sup> IV once on day 11, then 200 mg/m<sup>2</sup> IV once on day 21, then 250 mg/m<sup>2</sup> IV once on day 31, then 300 mg/m<sup>2</sup> IV once on day 41
 
−
**Given over 2 to 5 minutes (undiluted) or over 10 to 15 minutes (diluted).
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 31
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
====Supportive therapy, DS Arm====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> PO x 2 doses given 48 and 60 hours after the lumbar puncture on days 33, 34
 
−
'''8-week course, followed by:'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Delayed Intensification {{#subobject:17185g|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push/infusion over 1 to 15 minutes once per day on days 1, 8, 15
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4
 
−
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup> PO once per day on days 29 to 42
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup>/dose PO twice daily on days 1 to 7, 15 to 21 (10 mg/m<sup>2</sup>/day)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1 & 29
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
====Supportive therapy, DS Arm====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> PO x 2 doses given 48 and 60 hours after the lumbar puncture on days 3 to 4, 31 to 32
 
−
'''8-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Methotrexate_.26_Vincristine_2|MTX & Vincristine]] interim maintenance II
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, II (Methotrexate & Vincristine) {{#subobject:0ae09f|Regimen=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/PMC3138679/ Matloub et al. 2011 (COG CCG-1991)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Mercaptopurine.2C_Methotrexate.2C_Vincristine.2C_Dexamethasone_88|Mercaptopurine, MTX, Vincristine, Dexamethasone]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV once on day 1, then 150 mg/m<sup>2</sup> IV once on day 11, then 200 mg/m<sup>2</sup> IV once on day 21, then 250 mg/m<sup>2</sup> IV once on day 31, then 300 mg/m<sup>2</sup> IV once on day 41
 
−
**Given over 2 to 5 minutes (undiluted) or over 10 to 15 minutes (diluted)
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 31
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
====Supportive therapy, DS Arm====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> PO x 2 doses given 48 and 60 hours after the lumbar puncture on days 3 to 4, 33 to 34
 
−
'''8-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*COG AALL0932: [[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, Arm A and C (Vincristine/Dexamethasone Pulses) {{#subobject:0ae09f|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
'''For AR B-ALL patients, and LR-C Arm'''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, 57
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO twice daily on days 1 to 5, 29 to 33, 57 to 61 (6 mg/m<sup>2</sup>/day)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 1
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, Arm B and D (Vincristine/Dexamethasone Pulses) {{#subobject:0ae09f|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*Currently maintenance arm B and D are also treated with [[Methotrexate (MTX)]] PO at 20 mg/m<sup>2</sup> (decreased from the starting dose of 40 mg/m<sup>2</sup>) on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, 57
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO twice daily on days 1 to 5, 29 to 33, 57 to 61
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 1
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, Arm DS (Vincristine/Dexamethasone) {{#subobject:0ae09f|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
'''For DS AR B-ALL patients and DS B-LLy'''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice daily on days 1 to 5 (DO NOT TAPER)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 1
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Consolidation, Arm LR-M {{#subobject:0ae09f|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV on days 8, 29, 50, 71, 92, 113
 
−
Given as a 200 mg/m<sup>2</sup> bolus over 20 to 30 minutes followed by 800 mg/m<sup>2</sup> over 23.5 hours (initial bolus of 30 minutes) or 23 hours and 40 minutes (if initial bolus was over 20 minutes)
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 78, 85
 
−
*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 33
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice daily on days 15 to 21, 78 to 84
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> x 2 doses PO or IV (given 48 and 60 hours after the START of methotrexate infusion, continuing until methotrexate level < 0.2 μM) on days 9, 10, 30, 31, 51, 52, 72, 73, 93, 94, 114, 115
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on days 8, 29, 50, 71, 92,  113 (To be delivered within 6 hours of the beginning of the IV methotrexate infusion, -6hr to + 6 hr)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''19-week cycle'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, Arm LR-M {{#subobject:0ae09f|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
Methotrexate (MTX) DATES CHANGE DEPENDING ON CYCLE NUMBER
 
−
Cycles 1 and 4:
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 92, 99, 106
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 112 (NOTE: Higher 6-MP dose than in consolidation)
 
−
Cycles 2 and 5:
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO on days 1, 8, 15, 22, 29, 36, 43, 50, 64, 71, 78, 85, 92, 99, 106
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 112 (NOTE: Higher 6-MP dose than in consolidation)
 
−
Cycles 3 and 6:
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO on days 1, 8, 15, 22, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 106
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 112 (NOTE: Higher 6-MP dose than in consolidation)
 
−
Cycle 7:
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO on days 1, 8, 15, 29, 22, 36, 43, 50, 57, 64
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 70 (NOTE: Higher 6-MP dose than in consolidation)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO twice daily on days 1 to 7 (6 mg/m<sup>2</sup>/day, do not taper)
 
−
====CNS therapy, prophylaxis====
 
−
DATES CHANGE DEPENDING ON CYCLE NUMBER
 
−
Cycles 1 and 4:
 
−
*[[Methotrexate (MTX)]] IT once on day 1, 85
 
−
Cycles 2 and 5:
 
−
*[[Methotrexate (MTX)]] IT once on day 57
 
−
Cycles 3 and 6:
 
−
*[[Methotrexate (MTX)]] IT once on day 29
 
−
Cycle 7:
 
−
NO MTX IT on Cycle 7
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''16-week cycles until a total duration of therapy of 2.5 years from the date of diagnosis is reached for both boys and girls.'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, Arm LLy (Vincristine/Dexamethasone) {{#subobject:0ae09f|Regimen=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, 57 (4 Week Intervals)
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO twice daily on days 1 to 5, 29 to 33, 57 to 61 (6 mg/m<sup>2</sup>/day) (DO NOT TAPER)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 1
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''
 
−
</div></div>
 
−
===References===
 
−
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945
 
−
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274746/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930
 
  
−
==COG AALL1131 protocol==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
Patients < 10 years ONLY:
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 14
 
−
Patients ≥ 10 years ONLY:
 
−
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup> PO twice per day on days 1 to 28
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] by the following criteria:
 
−
**Ages 1 to 1.99: 30 mg IT once on day 1
 
−
**Ages 2 to 2.99: 50 mg IT once on day 1
 
−
**Age 3 and older: 70 mg IT once on day 1
 
−
CNS2 Patients will receive an additional dose of [[Cytarabine (Ara-C)]] IT on either day 4, 5, or 6, and then another dose of [[Cytarabine (Ara-C)]] IT on either day 11 or 12 according to the following dosing.
 
−
*[[Cytarabine (Ara-C)]] by the following criteria:
 
−
**Ages 1 to 1.99: 20 mg IT once
 
−
**Ages 2 to 2.99: 30 mg IT once
 
−
**Age 3 and older: 40 mg IT once
 
−
*[[Methotrexate (MTX)]] by the following criteria: (CNS3 also on Days 15 and 22)
 
−
**Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
 
−
**Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
 
−
**Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
 
−
**Age 9 and older: 15 mg IT once per day on days 8 & 29
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See protocol for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049
 
−
==COG AALL1131 protocol for HR B-ALL==
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Consolidation, Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on days 1, 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 15, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 14, 29 to 42
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, 22
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, with HD MTX {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
 
−
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 56
 
−
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, 43
 
−
**[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV infused over 30 minutes, then [[Methotrexate (MTX)]] 4,500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours
 
−
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of high dose [[Methotrexate (MTX)]]
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of high dose methotrexate infusion) on days 3 to 4, 17 to 18, 31 to 32, 45 to 46
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
When IT methotrexate therapy and high dose methotrexate are scheduled for the same day, deliver the IT methotrexate within 6 hours of the beginning of the IV methotrexate infusion. (hour -6 or +6, with 0 being the start of the methotrexate bolus).
 
−
'''63-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Delayed Intensification {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, 15
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 4, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 29 ONLY
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
 
−
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup> PO once per day on days 29 to 42
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 7, 15 to 21
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29, 36
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, HR B-ALL {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
Cycles 1-4
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, 57
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 to 4: 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 36, 43, 50, 57, 64, 71, 78
 
−
**Cycle 5 onwards: 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 to 5, 29 to 33, 57 to 61
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 to 4: IT once per day on days 1, 29
 
−
**Cycle 5 onwards: IT once per day on day 1
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-Week Cycles repeated until the total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcomes for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049
 
−
==COG AALL1131 protocol for VHR B-ALL==
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Consolidation {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 15, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1, 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes once daily on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 14, 29 to 42
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, 22 (Omit days 15 and 22 for CNS3 Patients)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, I with HD MTX {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 56
 
−
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, 43
 
−
**[[Methotrexate (MTX)]]500 mg/m<sup>2</sup> IV infused over 30 minutes, then [[Methotrexate (MTX)]] 4,500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours
 
−
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of high dose methotrexate.
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 to 4, 17 to 18, 31 to 32, 45 to 46
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''28-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Delayed Intensification {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, 15
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 29 ONLY
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
 
−
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup> PO once per day on days 29 to 42
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 7, 15 to 21
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on day 1, 29, 36
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, II with Capizzi MTX {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, 41
 
−
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV over 2 to 5 minutes (undiluted) or over 10 to 15 minutes (diluted) on days 1, 150 mg/m<sup>2</sup> on day 11, 200 mg/m<sup>2</sup> on day 21, 250 mg/m<sup>2</sup> on day 31, and 300 mg/m<sup>2</sup> on day 41
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 2, 22
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 31
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, VHR Arm {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
For Patients with CNS3 Disease
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, 57
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71, 78 (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX)
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 to 5, 29 to 33, 57 to 61
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcomes for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049
 
−
==COG AALL1131 protocol for Ph-like B-ALL (Dasatinib Arm)==
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Consolidation {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on days 1, 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes once daily on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 15, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 14, 29 to 42
 
−
*[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> (rounded to the nearest 5 mg, maximum dose of 140 mg/day) PO once daily on days 1 to 56
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, 22
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, with HD MTX {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
 
−
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 56.
 
−
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, 43
 
−
**[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV infused over 30 minutes, then [[Methotrexate (MTX)]] 4,500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours
 
−
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of high dose methotrexate
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of high dose [[Methotrexate (MTX)]] infusion) on days 3, 4, 17, 18, 31, 32, 45, 46
 
−
*[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> (rounded to the nearest 5 mg, maximum dose of 140 mg/day) PO once daily on days 1 to 63
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
When IT methotrexate therapy and high dose methotrexate are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV methotrexate infusion. (hour -6 or +6, with 0 being the start of the methotrexate bolus).
 
−
'''63-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Delayed Intensification {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, 15
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 4, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 29 ONLY
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
 
−
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup> PO once per day on days 29 to 42
 
−
*[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> (rounded to the nearest 5 mg, maximum dose of 140 mg/day) PO once daily on days 1 to 56
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 7, 15 to 21
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29, 36
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, II with Capizzi MTX {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, 41
 
−
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV over 2 to 5 minutes (undiluted) or over 10 to 15 minutes (diluted) on days 1, 150 mg/m<sup>2</sup> on day 11, 200 mg/m<sup>2</sup> on day 21, 250 mg/m<sup>2</sup> on day 31, and 300 mg/m<sup>2</sup> on day 41
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 2, 22
 
−
*[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> (rounded to the nearest 5 mg, maximum dose of 140 mg/day) PO once daily on days 1 to 56
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 31
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
For Patients with CNS3 Disease
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 84
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, 57
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71, 78 (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX)
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 to 5, 29 to 33, 57 to 61
 
−
====Targeted therapy====
 
−
*[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 84
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049
 
−
==COG AALL1131 protocol for DS HR B-ALL {{#subobject:088146|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Induction, Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
RER - M1 Marrow at Day 15
 
−
*Add [[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once on days 15
 
−
====Glucocorticoid therapy====
 
−
Patients < 10 years ONLY:
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28 (DO NOT TAPER)
 
−
Patients ≥ 10 years ONLY:
 
−
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup> PO twice per day on days 1 to 28 (DO NOT TAPER)
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 10, 11, 31, 32 (CNS3 also on days 17, 18, 24, 25)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**Ages 1 to 1.99: 30 mg IT once on day 1
 
−
**Ages 2 to 2.99: 50 mg IT once on day 1
 
−
**Age 3 and older: 70 mg IT once on day 1
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Ages 1 to 1.99: 8 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
 
−
**Ages 2 to 2.99: 10 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
 
−
**Ages 3 to 8.99: 12 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
 
−
**Age 9 and older: 15 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See protocol for details of treatment beyond induction
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Consolidation {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on days 1, 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 15, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 14, 29 to 42
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, 22
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
DS Arm
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 3, 4, 10, 11, 17, 18, 24, 25
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Interim Maintenance, with ID MTX {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
 
−
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup>/dose PO once per day on days 1 to 56
 
−
*Intermediate Dose [[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, 43
 
−
**[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV infused over 30 minutes, then [[Methotrexate (MTX)]] 1800 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours
 
−
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of high dose methotrexate
 
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 5 doses PO or IV (given at 30, 36, 42, 48, and 54 hours after the START of intermediate dose methotrexate infusion) on days 2, 3, 17, 18, 31, 32, 45, 46
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
When IT methotrexate therapy and high dose methotrexate are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV methotrexate infusion. (hour -6 or +6, with 0 being the start of the methotrexate bolus).
 
−
'''63-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Delayed Intensification {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, 15
 
−
*[[Pegaspargase (Oncaspar)]] 2,500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 4, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, 50
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 29 ONLY
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> SC or IV over 1 to 30 minutes on days 29 to 32, 36 to 39
 
−
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup> PO once per day on days 29 to 42
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 7, 15 to 21
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses PO or IV (given at 48, and 60 hours after the lumbar puncture) on days 3, 4, 31, 32, 38, 39
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 29, 36
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''56-Day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Maintenance, DS HR Arm {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
For Patients with CNS3 Disease
 
−
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 to 84
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on day 1 ONLY
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71, 78 (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX)
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup>/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation)
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Age
 
−
! style="width: 25%" |Dose
 
−
|-
 
−
|1 - 1.99
 
−
|8 mg
 
−
|-
 
−
|2 - 2.99
 
−
|10 mg
 
−
|-
 
−
|3 - 8.99
 
−
|12 mg
 
−
|-
 
−
|≥ 9
 
−
|15 mg
 
−
|}
 
−
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049
 
−
 
−
=Prephase=
 
−
==Methylprednisolone monotherapy {{#subobject:5gh1bb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:88fgh7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(15)00363-0 Place et al. 2015 (DFCI 05-001)]
 
−
|2005-2011
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1002/pbc.28719 Burns et al. 2020 (DFCI 11-001)]
 
−
|2012-2015
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Methylprednisolone (Solumedrol)]] 8 mg/m<sup>2</sup> IV three times per day on days 1 to 3
 
−
'''3-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*DFCI 05-001: [[#Doxorubicin.2C_L-Asparaginase.2C_Methotrexate.2C_Vincristine.2C_Methylprednisolone_88|Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Methylprednisolone]] versus [[#Doxorubicin.2C_Methotrexate.2C_Pegaspargase.2C_Vincristine.2C_Methylprednisolone|Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone]] induction
 
−
*DFCI 11-001: [[#Calaspargase.2C_Doxorubicin.2C_Methotrexate.2C_Vincristine.2C_Methylprednisolone_88|Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone]] versus [[#Doxorubicin.2C_Methotrexate.2C_Pegaspargase.2C_Vincristine.2C_Methylprednisolone|Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone]] induction
 
−
</div></div>
 
−
===References===
 
−
#'''DFCI 05-001:''' Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. Epub 2015 Nov 6. [https://doi.org/10.1016/s1470-2045(15)00363-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26549586/ PubMed] NCT00400946
 
−
##'''Pooled update:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed]
 
−
#'''DFCI 11-001:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed] NCT01574274
 
−
## '''Update:''' Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. Epub 2021 Jul 6. [https://doi.org/10.1200/jco.20.03692 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34228505/ PubMed]
 
−
==Prednisone monotherapy {{#subobject:8ca13b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2fd1d7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/127/17/2101.long Möricke et al. 2016 (AIEOP-BFM ALL 2000)]
 
−
|2000-2006
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 7
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 1
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#DOLP|Daunorubicin, L-Asparaginase, Vincristine, Prednisone]] versus [[#Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Dexamethasone_99|Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone]] induction
 
−
</div></div>
 
−
===References===
 
−
#'''AIEOP-BFM ALL 2000:''' Möricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Aricò M, Bartram CR, Attarbaschi A, Silvestri D, Beier R, Basso G, Ratei R, Kulozik AE, Lo Nigro L, Kremens B, Greiner J, Parasole R, Harbott J, Caruso R, von Stackelberg A, Barisone E, Rössig C, Conter V, Schrappe M. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016 Apr 28;127(17):2101-12. Epub 2016 Feb 17. [http://www.bloodjournal.org/content/127/17/2101.long link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/26888258 PubMed] NCT00430118; NCT00613457
 
−
==Vincristine & Prednisone {{#subobject:663781|Regimen=1}}==
 
−
VP: '''<u>V</u>'''incristine & '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:79fc67|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/51/3/425.long Sallan et al. 1978]
 
−
|1973-1977
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''Note: this regimen is of historic interest as an induction regimen; it is still occasionally used as pre-phase in patients too ill to get cytotoxic chemotherapy at time of diagnosis.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 21
 
−
'''21-day course'''
 
−
</div></div>
 
−
===References===
 
−
#Sallan SE, Cammita BM, Cassady JR, Nathan DG, Frei E 3rd. Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results. Blood. 1978 Mar;51(3):425-33. [http://www.bloodjournal.org/content/51/3/425.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/272207 PubMed]
 
−
=Upfront induction therapy=
 
−
==Calaspargase, Daunorubicin, Vincristine, Prednisone {{#subobject:1abca2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cf26ce|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/PMC4239306/ Angiolillo et al. 2014 (COG AALL07P4)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Randomized (E-RT-switch-ic)
 
−
|[[#Daunorubicin.2C_Pegaspargase.2C_Vincristine.2C_Prednisone_88|Daunorubicin, Pegaspargase, Vincristine, Prednisone]]
 
−
| style="background-color:#1a9850" |Longer half-life
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Calaspargase (Asparlas)]] 2500 units/m<sup>2</sup> IV once on day 4
 
−
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup> PO twice per day on days 1 to 28
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See protocol for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL07P4:''' Angiolillo AL, Schore RJ, Devidas M, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Keilani T, Lane AR, Loh ML, Reaman GH, Adamson PC, Wood B, Wood C, Zheng HW, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children's Oncology Group Study AALL07P4. J Clin Oncol. 2014 Dec 1;32(34):3874-82. Epub 2014 Oct 27. [https://doi.org/10.1200/JCO.2014.55.5763 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239306/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25348002 PubMed] NCT00671034
 
−
==Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:088146|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:98346f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
 
−
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 14
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**Ages 1 to 1.99: 30 mg IT once on day 1
 
−
**Ages 2 to 2.99: 50 mg IT once on day 1
 
−
**Age 3 and older: 70 mg IT once on day 1
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
 
−
**Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
 
−
**Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
 
−
**Age 9 and older: 15 mg IT once per day on days 8 & 29
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See protocol for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049
 
−
==DOLP {{#subobject:3c9897|Regimen=1}}==
 
−
DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisone
 
−
<br>DVPA: '''<u>D</u>'''aunorubicin, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone, '''<u>A</u>'''sparaginase
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 25/1.5/6000/60 {{#subobject:3fe1a2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254538/ Seibel et al. 2008 (COG CCG-1961)]
 
−
|1996-2002
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|[https://doi.org/10.1002/pbc.24149 Termuhlen et al. 2012 (COG A5971)]
 
−
|2000-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: COG A5971 was intended for patients with localized lymphoblastic lymphoma, of which 75% had B-cell immunophenotype. Exact days were not specified for the L-asparaginase; suggested days are similar to those used in other protocols. COG CCG-1961 did not specify a tapering schedule for prednisone, and did not cap vincristine.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 0, 7, 14, 21
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 0, 7, 14, 21
 
−
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IM once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 0 to 27, then tapered from days 28 to 38 (see note)
 
−
====CNS therapy====
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**Age 1-1.99 years: 30 mg IT once on day 0
 
−
**Age 2-2.99 years: 50 mg IT once on day 0
 
−
**Age 3 or greater: 70 mg IT once on day 0
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Age 1-1.99 years: 8 mg IT once per day on days 7 & 28
 
−
**Age 2-2.99 years: 10 mg IT once per day on days 7 & 28
 
−
**Age 3 or greater: 12 mg IT once per day on days 7 & 28
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*COG CCG-1961: Standard versus increased intensity post-remission therapy (see paper for details)
 
−
*COG A5971: Consolidation (see paper for details)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 30/1.5/5000/60 ("Phase A" of ALL-BFM 95; "Phase 1" of ALL IC-BFM 2002) {{#subobject:020017|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/9/4477.long Möricke et al. 2008 (ALL-BFM 95)]
 
−
|1995-2000
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.48.6522 Stary et al. 2013 (ALL IC-BFM 2002)]
 
−
|2002-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
''Note: see papers for details on dose adjustments based on risk. For example, in ALL IC-BFM 2002, days 22 & 29 of daunorubicin were omitted for standard risk B-cell precursor acute lymphoblastic leukemia.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22, 29
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29
 
−
*[[Asparaginase (Elspar)]] 5000 units IV over 60 minutes once per day on days 12, 15, 18, 21, 24, 27, 30, 33
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28, tapered over 9 days
 
−
====CNS therapy====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once per day on days 1, 12, 33
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See papers for details
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 30/1.5/10,000/60 ("Protocol I") {{#subobject:0ccc82|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/95/11/3310.long Schrappe et al. 2000 (ALL-BFM 90)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|[https://doi.org/10.1038/sj.leu.2402489 Kamps et al. 2002 (DCLSG ALL-8)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''Note: see papers for details on dose adjustments based on risk.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22, 29
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29
 
−
*[[Asparaginase (Elspar)]] 10,000 units IV over 60 minutes once per day on days 12, 15, 18, 21, 24, 27, 30, 33
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28
 
−
====CNS therapy====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once per day on days 1, 15, 29
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See papers for details
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 40/1.5/10,000/60 ("Induction Protocol I" of ALL-BFM 86) {{#subobject:6ad40d|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/84/9/3122.long Reiter et al. 1994 (ALL-BFM 86)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[http://www.bloodjournal.org/content/94/4/1226.long Kamps et al. 1999 (DCLSG ALL-7)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 40 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29
 
−
*[[Asparaginase (Elspar)]] 10,000 units/m<sup>2</sup> IV once per day on days 19, 22, 25, 28, 31, 34, 37, 40
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28
 
−
'''6-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Induction phase II (see papers for details)
 
−
</div></div>
 
−
===References===
 
−
#'''ALL-BFM 86:''' Reiter A, Schrappe M, Ludwig WD, Hiddemann W, Sauter S, Henze G, Zimmermann M, Lampert F, Havers W, Niethammer D, Odenwald E, Ritter J, Mann G, Welte K, Gadner H, Riehm H. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients: results and conclusions of the multicenter trial ALL-BFM 86. Blood. 1994 Nov 1;84(9):3122-33. [http://www.bloodjournal.org/content/84/9/3122.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7949185 PubMed]
 
−
#'''DCLSG ALL-7:''' Kamps WA, Bökkerink JP, Hählen K, Hermans J, Riehm H, Gadner H, Schrappe M, Slater R, van den Berg-de Ruiter E, Smets LA, de Vaan GA, Weening RS, van Weerden JF, van Wering ER, den der Does-van den Berg A. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group protocol ALL-7 (1988-1991). Blood. 1999 Aug 15;94(4):1226-36. [http://www.bloodjournal.org/content/94/4/1226.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10438710 PubMed]
 
−
#'''ALL-BFM 90:''' Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H; German-Austrian-Swiss ALL-BFM Study Group. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood. 2000 Jun 1;95(11):3310-22. [http://www.bloodjournal.org/content/95/11/3310.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10828010 PubMed]
 
−
##'''Pooled subgroup analysis:''' Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. [https://doi.org/10.1200/JCO.2006.06.2679 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17179108 PubMed]
 
−
#'''DCLSG ALL-8:''' Kamps WA, Bökkerink JP, Hakvoort-Cammel FG, Veerman AJ, Weening RS, van Wering ER, van Weerden JF, Hermans J, Slater R, van den Berg E, Kroes WG, van der Does-van den Berg A. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996). Leukemia. 2002 Jun;16(6):1099-111. [https://doi.org/10.1038/sj.leu.2402489 link to original article] '''refers to ALL-BFM 90 protocol''' [https://pubmed.ncbi.nlm.nih.gov/12040440 PubMed]
 
−
#'''COG CCG-1961:''' Seibel NL, Steinherz PG, Sather HN, Nachman JB, Delaat C, Ettinger LJ, Freyer DR, Mattano LA Jr, Hastings CA, Rubin CM, Bertolone K, Franklin JL, Heerema NA, Mitchell TL, Pyesmany AF, La MK, Edens C, Gaynon PS. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 1;111(5):2548-55. [http://www.bloodjournal.org/content/111/5/2548.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254538/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18039957 PubMed] NCT00002812
 
−
#'''ALL-BFM 95:''' Möricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dördelmann M, Löning L, Beier R, Ludwig WD, Ratei R, Harbott J, Boos J, Mann G, Niggli F, Feldges A, Henze G, Welte K, Beck JD, Klingebiel T, Niemeyer C, Zintl F, Bode U, Urban C, Wehinger H, Niethammer D, Riehm H, Schrappe M; German-Austrian-Swiss ALL-BFM Study Group. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008 May 1;111(9):4477-89. Epub 2008 Feb 19. Erratum in: Blood. 2009 Apr 30;113(18):4478. Dosage error in article text. [http://www.bloodjournal.org/content/111/9/4477.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18285545 PubMed]
 
−
##'''Pooled subgroup analysis:''' Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. [https://doi.org/10.1200/JCO.2006.06.2679 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17179108 PubMed]
 
−
#'''COG A5971:''' Termuhlen AM, Smith LM, Perkins SL, Lones M, Finlay JL, Weinstein H, Gross TG, Abromowitch M. Outcome of newly diagnosed children and adolescents with localized lymphoblastic lymphoma treated on Children's Oncology Group trial A5971: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Dec 15;59(7):1229-33. Epub 2012 Apr 5. [https://doi.org/10.1002/pbc.24149 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22488718/ PubMed] NCT00004228
 
−
#'''ALL IC-BFM 2002:''' Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, Konja J, Kaiserova E, Kowalczyk J, Kovacs G, Li CK, Magyarosy E, Popa A, Stark B, Jabali Y, Trka J, Hrusak O, Riehm H, Masera G, Schrappe M. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014 Jan 20;32(3):174-84. Epub 2013 Dec 16. [https://doi.org/10.1200/jco.2013.48.6522 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24344215/ PubMed] NCT00764907
 
−
==DOLP (Prednisolone) {{#subobject:3c7jg7|Regimen=1}}==
 
−
DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 30/10,000/1.5/60 {{#subobject:087cg2|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/PMC2904579/ de Moerloose et al. 2010 (EORTC CLG 58951)]
 
−
|1999-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Dexamethasone_99|Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
''Note: see paper for details on CNS therapy and dose adjustments based on risk; these instructions include a 7-day pre-phase and are for AR1 patients.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 30 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29
 
−
*[[Asparaginase (Elspar)]] 10,000 units (route not specified) once per day on days 12, 15, 18, 22, 25, 29, 32, 35
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28, then tapered over 9 days
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 45/6000/1.5/40 {{#subobject:b39731|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/014067369292103M Chessells et al. 1992 (UK MRC ALLX)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: exact days for L-asparaginase were not specified in the protocol.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
 
−
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> SC once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 28
 
−
'''29-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Intensification (randomized) or [[#Cyclophosphamide_.26_TBI.2C_then_allo_HSCT|Cy/TBI with allo HSCT]], depending on donor availability
 
−
</div></div>
 
−
===References===
 
−
#'''UK MRC ALLX:''' Chessells JM, Bailey C, Wheeler K, Richards SM. Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia in first remission: experience in MRC UKALL X. Lancet. 1992 Sep 5;340(8819):565-8. [https://doi.org/10.1016/014067369292103M link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1355153 PubMed]
 
−
##'''Update:''' Chessells JM, Bailey C, Richards SM; Medical Research Council Working Party on Childhood Leukaemia. Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X. Lancet. 1995 Jan 21;345(8943):143-8. [https://doi.org/10.1016/S0140673695901647 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7823668 PubMed]
 
−
#'''EORTC CLG 58951:''' De Moerloose B, Suciu S, Bertrand Y, Mazingue F, Robert A, Uyttebroeck A, Yakouben K, Ferster A, Margueritte G, Lutz P, Munzer M, Sirvent N, Norton L, Boutard P, Plantaz D, Millot F, Philippet P, Baila L, Benoit Y, Otten J; Children's Leukemia Group of the European Organisation for Research and Treatment of Cancer. Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951. Blood. 2010 Jul 8;116(1):36-44. Epub 2010 Apr 20. [http://www.bloodjournal.org/content/116/1/36.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904579/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20407035 PubMed] NCT00003728
 
−
##'''Update:''' Domenech C, Suciu S, De Moerloose B, Mazingue F, Plat G, Ferster A, Uyttebroeck A, Sirvent N, Lutz P, Yakouben K, Munzer M, Röhrlich P, Plantaz D, Millot F, Philippet P, Dastugue N, Girard S, Cavé H, Benoit Y, Bertrand Y; Children's Leukemia Group (CLG) of European Organisation for Research and Treatment of Cancer. Dexamethasone (6 mg/m<sup>2</sup>/day) and prednisolone (60 mg/m<sup>2</sup>/day) were equally effective as induction therapy for childhood acute lymphoblastic leukemia in the EORTC CLG 58951 randomized trial. Haematologica. 2014 Jul;99(7):1220-7. Epub 2014 Apr 11. [http://www.haematologica.org/content/99/7/1220.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24727815 PubMed]
 
−
##'''Update:''' Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poirée M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cavé H, Rohrlich P, Bertrand Y, Benoit Y; Children's Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer. Prolonged versus standard native E coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951. Haematologica. 2017 Oct;102(10):1727-1738. Epub 2017 Jul 27. [http://www.haematologica.org/content/102/10/1727.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622857/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28751566 PubMed]
 
−
==Doxorubicin, Mercaptopurine, Pegaspargase, Vincristine, Prednisolone {{#subobject:127ca2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:nc303e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.18.01877 Albertsen et al. 2019 (NOPHO ALL2008)]
 
−
|2008-2016
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: See protocol for initiation dependencies of 6-MP and pegaspargase.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 22
 
−
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup> PO once per day on days 30 to 35
 
−
*[[Pegaspargase (Oncaspar)]] 1000 units/m<sup>2</sup> IM once on day 30
 
−
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 
−
**Younger than 18: 2 mg/m<sup>2</sup> (maximum dose of 2.5 mg) IV once per day on days 1, 8, 15, 22, 29
 
−
**18 or older: 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 20 mg/m<sup>2</sup> PO three times per day on days 1 to 29, then 10 mg/m<sup>2</sup> PO three times per day on days 30 to 32, then 5 mg/m<sup>2</sup> PO three times per day on days 33 to 35, then 2.5 mg/m<sup>2</sup> PO three times per day on days 36 to 38
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Ages 1 to 1.9: 8 mg IT once per day on days 1, 8, 15, 29
 
−
**Ages 2 to 2.9: 10 mg IT once per day on days 1, 8, 15, 29
 
−
**Age 3 and older: 12 mg IT once per day on days 1, 8, 15, 29
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See protocol for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''NOPHO ALL2008:''' Albertsen BK, Grell K, Abrahamsson J, Lund B, Vettenranta K, Jónsson ÓG, Frandsen TL, Wolthers BO, Heyman M, Schmiegelow K. Intermittent versus continuous PEG-asparaginase to reduce asparaginase-associated toxicities: a NOPHO ALL2008 randomized study. J Clin Oncol. 2019 Jul 1;37(19):1638-1646. Epub 2019 Apr 12. [https://doi.org/10.1200/JCO.18.01877 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30978155 PubMed] NCT00819351
 
−
 
−
==Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone {{#subobject:h1gtbb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:hgu1h7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 17%" |Study
 
−
! style="width: 15%" |Years of enrollment
 
−
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 17%" |Comparator
 
−
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(15)00363-0 Place et al. 2015 (DFCI 05-001)]
 
−
|2005-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin.2C_L-Asparaginase.2C_Methotrexate.2C_Vincristine.2C_Methylprednisolone_88|Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Methylprednisolone]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoint of DFS
 
−
| style="background-color:#1a9850" |Less anxiety
 
−
|-
 
−
|[https://doi.org/10.1002/pbc.28719 Burns et al. 2020 (DFCI 11-001)]
 
−
|2012-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Calaspargase.2C_Doxorubicin.2C_Methotrexate.2C_Vincristine.2C_Methylprednisolone_99|Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|
 
−
|-
 
−
|}
 
−
''Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001. Day numbering takes into account the pre-phase.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Methylprednisolone_monotherapy|Methylprednisolone]] pre-phase
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 4 & 5
 
−
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once on day 6
 
−
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once on day 7
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 4, 11, 18, 25
 
−
====Glucocorticoid therapy====
 
−
*[[Methylprednisolone (Solumedrol)]] 8 mg/m<sup>2</sup> IV three times per day on days 4 to 32
 
−
====Supportive therapy====
 
−
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 4 & 5
 
−
'''28-day course'''
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT once per day on days 1 & 18
 
−
**Day 18 dose is admixed with MTX and HC
 
−
*[[Methotrexate (MTX)]] IT once per day on days 18 & 32
 
−
**Day 18 dose is admixed with Ara-C and HC
 
−
*[[Hydrocortisone (Cortef)]] IT once on day 18, admixed with Ara-C and MTX
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Doxorubicin.2C_Mercaptopurine.2C_Methotrexate.2C_Vincristine|Doxorubicin, Mercaptopurine, Methotrexate, Vincristine]] consolidation (IA)
 
−
</div></div>
 
−
===References===
 
−
#'''DFCI 05-001:''' Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. Epub 2015 Nov 6. [https://doi.org/10.1016/s1470-2045(15)00363-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26549586/ PubMed] NCT00400946
 
−
##'''Pooled update:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed]
 
−
#'''DFCI 11-001:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed] NCT01574274
 
−
## '''Update:''' Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. Epub 2021 Jul 6. [https://doi.org/10.1200/jco.20.03692 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34228505/ PubMed]
 
−
==Pegaspargase, Vincristine, Dexamethasone {{#subobject:15hgu1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e8uyt1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ Maloney et al. 2019 (COG AALL0331)]
 
−
|2005-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: there are very minor differences in timing between protocols; see papers for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once on day 4
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO twice per day on days 1 to 28
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] IT once at some point between days -2 and 1
 
−
*[[Methotrexate (MTX)]] IT once per day on days 8 & 29
 
−
'''35-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*COG AALL0331, M2 marrow or M1 marrow with MRD of at least 1% at day 29: Extended induction
 
−
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL0331:''' Maloney KW, Devidas M, Wang C, Mattano LA, Friedmann AM, Buckley P, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Kadan-Lottick N, Loh ML, Matloub YH, Marshall DT, Stork LC, Raetz EA, Wood B, Hunger SP, Carroll WL, Winick NJ. Outcome in Children With Standard-Risk B-Cell Acute Lymphoblastic Leukemia: Results of Children's Oncology Group Trial AALL0331. J Clin Oncol. 2020 Feb 20;38(6):602-612. Epub 2019 Dec 11. [https://doi.org/10.1200/jco.19.01086 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31825704/ PubMed] NCT00103285
 
−
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930
 
−
==Pegaspargase, Vincristine, Prednisone {{#subobject:158722|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e8uhb3|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/99/6/1986.long Avramis et al. 2002 (CCG 1962)]
 
−
|1997-1998
 
−
| style="background-color:#1a9851" |Randomized (E-RT-switch-ic)
 
−
|[[B-cell_acute_lymphoblastic_leukemia_-_historical#L-Asparaginase.2C_Vincristine.2C_Prednisone|L-Asparaginase, Vincristine, Prednisone]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoint of EFS
 
−
|-
 
−
|}
 
−
''Note: the primary endpoint of CCG 1962 was incidence of high-titer ASNase antibodies in the first dose intensification, which is neither an efficacy nor a toxicity endpoint.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Pegaspargase (Oncaspar)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See protocol for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''CCG 1962:''' Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, Ettinger AG, Ettinger LJ, Franklin J, Gaynon PS, Hilden JM, Lange B, Majlessipour F, Mathew P, Needle M, Neglia J, Reaman G, Holcenberg JS, Stork L. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood. 2002 Mar 15;99(6):1986-94. Erratum in: Blood 2002 Sep 1;100(5):1531. [http://www.bloodjournal.org/content/99/6/1986.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11877270 PubMed]
 
−
=Early intensification therapy=
 
−
==Cyclophosphamide, Etoposide, Methotrexate {{#subobject:6ahzn6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:16fxc9|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/pmc5145261/ Dreyer et al. 2014 (COG P9407)]
 
−
|2001-2006
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1038/s41375-021-01177-6 Brown et al. 2021 (COG AALL0631)]
 
−
|2008-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide.2C_Etoposide.2C_Lestaurtinib.2C_Methotrexate_77|Cyclophosphamide, Etoposide, Lestaurtinib, Methotrexate]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*COG AALL0631: KMT2A rearrangement
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV over 30 minutes once per day on days 15 to 19
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 15 to 19
 
−
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV over 20 minutes, then 3800 mg/m<sup>2</sup> IV continuous infusion over 23 hours and 40 minutes on days 1 & 8 (total dose: 8000 mg/m<sup>2</sup>)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Reinduction
 
−
</div></div>
 
−
===References===
 
−
#'''COG P9407:''' Dreyer ZE, Hilden JM, Jones TL, Devidas M, Winick NJ, Willman CL, Harvey RC, Chen IM, Behm FG, Pullen J, Wood BL, Carroll AJ, Heerema NA, Felix CA, Robinson B, Reaman GH, Salzer WL, Hunger SP, Carroll WL, Camitta BM. Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3). Pediatr Blood Cancer. 2015 Mar;62(3):419-26. Epub 2014 Nov 14. [https://doi.org/10.1002/pbc.25322 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5145261/ link to PMC article]  [https://pubmed.ncbi.nlm.nih.gov/25399948/ PubMed] NCT00002756
 
−
#'''COG AALL0631:''' Brown PA, Kairalla JA, Hilden JM, Dreyer ZE, Carroll AJ, Heerema NA, Wang C, Devidas M, Gore L, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Borowitz MJ, Small D, Loh ML, Hunger SP. FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children's Oncology Group trial AALL0631. Leukemia. 2021 May;35(5):1279-1290. Epub 2021 Feb 23. Erratum in: Leukemia. 2021 Apr 12. [https://doi.org/10.1038/s41375-021-01177-6 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33623141/ PubMed] NCT00557193
 
−
 
−
==Mercaptopurine & Methotrexate {{#subobject:6ad6d6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5b0ec9|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.1998.16.1.246 Mahoney et al. 1998 (POG 9005)]
 
−
|1991-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]; LDMTX/IVMP
 
−
| style="background-color:#91cf60" |Seems to have superior CCR
 
−
|-
 
−
|[https://www.nature.com/articles/2402132 Lauer et al. 2001 (POG 9006)]
 
−
|1991-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Intensive chemotherapy
 
−
| style="background-color:#fee08b" |Might have inferior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*POG 9006: [[#DOLP|DOLP]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]]
 
−
*[[Methotrexate (MTX)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*POG 9006: [[#Mercaptopurine_.26_Methotrexate_2|6-MP & MTX]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''POG 9005:''' Mahoney DH Jr, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP, Camitta B. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III trial. J Clin Oncol. 1998 Jan;16(1):246-54. [https://doi.org/10.1200/JCO.1998.16.1.246 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9440749 PubMed]
 
−
#'''POG 9006:''' Lauer SJ, Shuster JJ, Mahoney DH Jr, Winick N, Toledano S, Munoz L, Kiefer G, Pullen JD, Steuber CP, Camitta BM. A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial. Leukemia. 2001 Jul;15(7):1038-45. [https://www.nature.com/articles/2402132 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11455971 PubMed]
 
−
=Consolidation after upfront therapy (including post-remission therapy)=
 
−
''Note that many of these regimens are complex and as such will be referred to by their study name, not by the individual drug names. This is also a phase of treatment often referred to as post-remission or postinduction therapy.''
 
−
==AALL0232 consolidation {{#subobject:065gg9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:342b6d|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ Larsen et al. 2016 (COG AALL0232)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 4, 8 to 11, 29 to 32, 36 to 39
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 14, 29 to 42
 
−
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IM or IV once per day on days 15 & 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
 
−
'''50-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*6-MP, Capizzi MTX, Pegaspargase, Vincristine interim maintenance versus [[#Mercaptopurine.2C_Methotrexate.2C_Vincristine_2|6-MP, HD-MTX, Vincristine interim]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL0232:''' Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, Mattano LA Jr, Cole C, Eicher A, Haugan M, Sorenson M, Heerema NA, Carroll AA, Gastier-Foster JM, Borowitz MJ, Wood BL, Willman CL, Winick NJ, Hunger SP, Carroll WL. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232. J Clin Oncol. 2016 Jul 10;34(20):2380-8. Epub 2016 Apr 25. [https://doi.org/10.1200/JCO.2015.62.4544 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27114587 PubMed] NCT00075725
 
−
==Augmented BFM consolidation {{#subobject:065ff9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:687b6d|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/NEJM199806043382304 Nachman et al. 1998]
 
−
|1991-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|Standard BFM consolidation
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
''Note: Unlikely to be completed, but of historic interest.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Cytarabine (Ara-C)]]
 
−
*[[Asparaginase (Elspar)]]
 
−
*[[Mercaptopurine (6-MP)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
</div></div>
 
−
===References===
 
−
#Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN, Wolff L, Uckun FM, Gaynon PS. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med. 1998 Jun 4;338(23):1663-71. [https://doi.org/10.1056/NEJM199806043382304 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9614257 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: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/54/2/468.long Thomas et al. 1979]
 
−
|1976-1977
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|6ca28d}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. [http://www.bloodjournal.org/content/54/2/468.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/378292 PubMed]
 
−
==Etoposide & TBI, then allo HSCT {{#subobject:b389e1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:45f841|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/10.1016/S014067360566998X Balduzzi et al. 2005]
 
−
|1995-2000
 
−
| style="background-color:#1a9851" |Quasi-randomized
 
−
|Chemotherapy
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2014.58.9747 Peters et al. 2015 (ALL-SCT-BFM 2003)]
 
−
|2003-2011
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|45f841}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. [https://doi.org/10.1016/S014067360566998X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16112299 PubMed]
 
−
#'''ALL-SCT-BFM-2003:''' Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. [https://doi.org/10.1200/jco.2014.58.9747 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25753432 PubMed] NCT01423747
 
−
==Mercaptopurine & Vincristine {{#subobject:171gc1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1ygvt1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Pegaspargase.2C_Vincristine.2C_Dexamethasone|Pegaspargase, Vincristine, Dexamethasone]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/day PO on days 1 to 28
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine]] interim maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930
 
−
=Interim maintenance=
 
−
==Mercaptopurine, Methotrexate, Vincristine {{#subobject:72025a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b9e09c|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/PMC4981974/ Larsen et al. 2016 (COG AALL0232)]
 
−
|2004-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Mercaptopurine.2C_Methotrexate.2C_Pegaspargase.2C_Vincristine_88|6-MP, Capizzi MTX, Pegaspargase, Vincristine]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 56
 
−
*[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV once per day on days 1, 15, 29, 43
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
 
−
====CNS therapy====
 
−
*[[Methotrexate (MTX)]] once per day on days 1 & 29
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL0232:''' Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, Mattano LA Jr, Cole C, Eicher A, Haugan M, Sorenson M, Heerema NA, Carroll AA, Gastier-Foster JM, Borowitz MJ, Wood BL, Willman CL, Winick NJ, Hunger SP, Carroll WL. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232. J Clin Oncol. 2016 Jul 10;34(20):2380-8. Epub 2016 Apr 25. [https://doi.org/10.1200/JCO.2015.62.4544 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27114587 PubMed] NCT00075725
 
−
==Methotrexate & Vincristine {{#subobject:0ae09f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:57f39d|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/PMC3138679/ Matloub et al. 2011 (COG CCG-1991)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Mercaptopurine.2C_Methotrexate.2C_Vincristine.2C_Dexamethasone_88|6-MP, MTX, Vincristine, Dexamethasone]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV once on day 1, then 150 mg/m<sup>2</sup> IV once on day 11, then 200 mg/m<sup>2</sup> IV once on day 21, then 250 mg/m<sup>2</sup> IV once on day 31, then 300 mg/m<sup>2</sup> IV once on day 41
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once on day 31
 
−
'''8-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*COG AALL0932: [[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]
 
−
</div></div>
 
−
===References===
 
−
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945
 
−
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930
 
−
=Delayed intensification=
 
−
==AALL0932 delayed intensification {{#subobject:17185g|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1y47gc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim]] maintenance
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 29
 
−
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV on days 29 to 32, 36 to 39
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once on day 4
 
−
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO on days 29 to 42
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 1 to 7, 15 to 21
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1 & 29
 
−
'''8-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Methotrexate_.26_Vincristine_2|MTX & Vincristine]] interim maintenance II
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930
 
−
=Interim maintenance II=
 
−
==Methotrexate & Vincristine {{#subobject:ajbz5g|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:18guaz|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]
 
−
|2010-2018
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: starting dose of the systemic MTX is 2/3 of the MTD from interim maintenance I; dosage below assumes that the final maximum dose was tolerated.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once on day 11, then 300 mg/m<sup>2</sup> IV once on day 21, then 350 mg/m<sup>2</sup> IV once on day 31, then 400 mg/m<sup>2</sup> IV once on day 41
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] IT once per day on days 1 & 31
 
−
'''8-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Randomization to one of four maintenance arms; see paper for details.
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930
 
−
=Maintenance after upfront therapy=
 
−
==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e46d92|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.2001.19.7.1935 Millot et al. 2001 (EORTC 58881)]
 
−
|1990-1996
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Mercaptopurine_.26_Methotrexate_2|6-MP & MTX]]; IV 6-MP & PO MTX
 
−
| style="background-color:#1a9850" |Superior DFS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(07)60073-7 Conter et al. 2007 (I-BFM-SG IR ALL)]
 
−
|1995-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#D-OMP_99|D-OMP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for EORTC 58881 is based on the 2005 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*I-BFM-SG IR ALL: BFM re-induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on day 1
 
−
'''7-day cycle for 74 cycles or a total of 2 years from start of treatment'''
 
−
</div></div>
 
−
===References===
 
−
#'''EORTC 58881:''' Millot F, Suciu S, Philippe N, Benoit Y, Mazingue F, Uyttebroeck A, Lutz P, Mechinaud F, Robert A, Boutard P, Marguerite G, Ferster A, Plouvier E, Rialland X, Behard C, Plantaz D, Dresse MF, Philippet P, Norton L, Thyss A, Dastugue N, Waterkeyn C, Vilmer E, Otten J; Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer. Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organisation for Research and Treatment of Cancer 58881 randomized phase III trial. J Clin Oncol. 2001 Apr 1;19(7):1935-42. [https://doi.org/10.1200/JCO.2001.19.7.1935 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11283125 PubMed]
 
−
##'''Update:''' Duval M, Suciu S, Ferster A, Rialland X, Nelken B, Lutz P, Benoit Y, Robert A, Manel AM, Vilmer E, Otten J, Philippe N. Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial. Blood. 2002 Apr 15;99(8):2734-9. [http://www.bloodjournal.org/content/99/8/2734.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11929760 PubMed]
 
−
##'''Update:''' van der Werff Ten Bosch J, Suciu S, Thyss A, Bertrand Y, Norton L, Mazingue F, Uyttebroeck A, Lutz P, Robert A, Boutard P, Ferster A, Plouvier E, Maes P, Munzer M, Plantaz D, Dresse MF, Philippet P, Sirvent N, Waterkeyn C, Vilmer E, Philippe N, Otten J. Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG. Leukemia. 2005 May;19(5):721-6. [https://www.nature.com/articles/2403689 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15744348 PubMed]
 
−
#'''I-BFM-SG IR ALL:''' Conter V, Valsecchi MG, Silvestri D, Campbell M, Dibar E, Magyarosy E, Gadner H, Stary J, Benoit Y, Zimmermann M, Reiter A, Riehm H, Masera G, Schrappe M. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet. 2007 Jan 13;369(9556):123-31. [https://doi.org/10.1016/S0140-6736(07)60073-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17223475 PubMed] NCT00411541
 
−
==Observation==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| 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/PMC8416799/ Yang et al. 2021 (CCCG-ALL-2015)]
 
−
|2015-2020
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Vincristine_.26_Dexamethasone_88|Vincristine & Dexamethasone]]
 
−
| style="background-color:#eeee01" |Non-inferior EFS60
 
−
|-
 
−
|}
 
−
''No active maintenance treatment beyond 1 year. Patients in this study were required to be in continuous remission for 1 year after initial treatment.''
 
−
</div></div>
 
−
===References===
 
−
#'''CCCG-ALL-2015:''' Yang W, Cai J, Shen S, Gao J, Yu J, Hu S, Jiang H, Fang Y, Liang C, Ju X, Wu X, Zhai X, Tian X, Wang N, Liu A, Jiang H, Jin R, Sun L, Yang M, Leung AWK, Pan K, Zhang Y, Chen J, Zhu Y, Zhang H, Li C, Yang JJ, Cheng C, Li CK, Tang J, Zhu X, Pui CH. Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021 Sep;22(9):1322-1332. Epub 2021 Jul 27. [https://doi.org/10.1016/s1470-2045(21)00328-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416799/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34329606/ PubMed] ChiCTR-IPR-14005706
 
−
=Relapsed or refractory=
 
−
==Blinatumomab monotherapy {{#subobject:e7b2c6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fd494b|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.67.3301 von Stackelberg et al. 2016 (MT103-205)]
 
−
|2012-2014
 
−
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
−
|-
 
−
|}
 
−
''Note: this is the MTD of a phase I/II trial enrolling children under the age of 18.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Blinatumomab (Blincyto)]] as follows:
 
−
**Cycle 1: 5 mcg/day IV continuous infusion over 7 days, started on day 1, then 15 mcg/day IV continuous infusion over 21 days, started on day 8 (total dose: 350 mcg)
 
−
**Cycles 2 to 5: 28 mcg/day IV continuous infusion over 28 days, started on day 1 (total dose per cycle: 784 mcg)
 
−
'''42-day cycle for up to 5 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MT103-205:''' von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. [https://doi.org/10.1200/JCO.2016.67.3301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27998223 PubMed] NCT01471782
 
−
==CCE {{#subobject:f74969|Regimen=1}}==
 
−
CCE: '''<u>C</u>'''lofarabine, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:24f55b|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2009.07882.x Locatelli et al. 2009]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''Note: Patients in this study were pediatric: ≤ 15 years old at diagnosis and ≤ 21 years old at time of treatment. No patients had CNS disease at time of treatment, and no patients received CNS prophylaxis.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, given first
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Prophylactic [[:Category:Steroids|steroids]] used for patients with greater than 30 x 10<sup>9</sup> blasts/L in the peripheral blood prior to treatment
 
−
'''5-day course'''
 
−
''2 out of 25 patients received a second course of CCE as consolidation therapy. Responding patients were given allogeneic HSCT if a suitable donor was immediately available or were given consolidation courses of chemotherapy including multiple agents active against ALL cells, chosen according to the treating physician's preference."''
 
−
</div></div>
 
−
 
−
===References===
 
−
#Locatelli F, Testi AM, Bernardo ME, Rizzari C, Bertaina A, Merli P, Pession A, Giraldi E, Parasole R, Barberi W, Zecca M. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol. 2009 Nov;147(3):371-8. Epub 2009 Aug 29. [https://doi.org/10.1111/j.1365-2141.2009.07882.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19747360 PubMed]
 
−
==Clofarabine monotherapy {{#subobject:6befdc|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fc17b2|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/3/784.long Jeha et al. 2003]
 
−
|2000-2002
 
−
| style="background-color:#ffffbe" |Phase 1, <20 pts (RT)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.03.8554 Jeha et al. 2006 (CLO212)]
 
−
|2002-2004
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
''Note: this dose was the MTD in Jeha et al. 2003.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Clofarabine (Clolar)]] 52 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
'''2- to 6-week cycles, depending on response count recovery'''
 
−
</div></div>
 
−
===References===
 
−
#Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R, Rytting M, Brandt M, Keating M, Plunkett W, Kantarjian H. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004 Feb 1;103(3):784-9. Epub 2003 Oct 9. [http://www.bloodjournal.org/content/103/3/784.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/14551141 PubMed]
 
−
#'''CLO212:''' Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V, Luchtman-Jones L, Rytting M, Bomgaars LR, Rheingold S, Ritchey K, Albano E, Arceci RJ, Goldman S, Griffin T, Altman A, Gordon B, Steinherz L, Weitman S, Steinherz P. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006 Apr 20;24(12):1917-23. [https://doi.org/10.1200/JCO.2005.03.8554 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16622268 PubMed] NCT00042341
 
−
==DOLP {{#subobject:8804f2|Regimen=1}}==
 
−
DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a6fef6|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198607313150501 Rivera et al. 1986]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Asparaginase (Elspar)]]
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#Rivera GK, Buchanan G, Boyett JM, Camitta B, Ochs J, Kalwinsky D, Amylon M, Vietti TJ, Crist WM; Pediatric Oncology Group. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse: a Pediatric Oncology Group study. N Engl J Med. 1986 Jul 31;315(5):273-8. [https://doi.org/10.1056/NEJM198607313150501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3523250 PubMed]
 
−
==Doxorubicin, Pegaspargase, Vincristine, Prednisone {{#subobject:1265yg|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3gt03e|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/10.1182/blood.V96.5.1709 Abshire et al. 2000 (POG 9310)]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2654313/ Raetz et al. 2008 (COG AALL01P2)]
 
−
|2003-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7776266/ Lew et al. 2021 (COG AALL0433)]
 
−
|2007-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin.2C_Pegaspargase.2C_Vincristine.2C_Prednisone|Doxorubicin, Pegaspargase, Vincristine, Prednisone]]; high-dose vincristine
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''Note: This is "Block 1" of re-induction. Randomization in COG AALL0433 was discontinued early due to high rates of neuropathy in the experimental arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IM once per day on days 2, 9, 16, 23
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 29
 
−
====CNS therapy, prophylaxis (CNS-)====
 
−
*[[Methotrexate (MTX)]] once per day on days 8 & 29
 
−
====CNS therapy, treatment (CNS+)====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Cytarabine (Ara-C)]]
 
−
*[[Hydrocortisone (Cortef)]]
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See papers for details of treatment beyond induction block 1
 
−
</div></div>
 
−
===References===
 
−
#'''POG 9310:''' Abshire TC, Pollock BH, Billett AL, Bradley P, Buchanan GR. Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood. 2000 Sep 1;96(5):1709-15. [https://doi.org/10.1182/blood.V96.5.1709 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10961868/ PubMed]
 
−
#'''COG AALL01P2:''' Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, Camitta BM, Gaynon PS, Carroll WL. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected]. J Clin Oncol. 2008 Aug 20;26(24):3971-8. Erratum in: J Clin Oncol. 2008 Oct 1;26(28): 4697. [https://doi.org/10.1200/jco.2008.16.1414 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2654313/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18711187/ PubMed] NCT00049569
 
−
#'''COG AALL0433:''' Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2021 Jan 1;106(1):46-55. [https://doi.org/10.3324/haematol.2019.237230 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7776266/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/32001530/ PubMed] NCT00381680
 
−
==Inotuzumab ozogamicin monotherapy {{#subobject:d90806|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8be9f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |Years of enrollment
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70386-2 Kantarjian et al. 2012 (MDACC 2009-0872)]
 
−
|2010-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Inotuzumab ozogamicin (Besponsa)]] 0.8 mg/m<sup>2</sup> IV once on day 1, then 0.5 mg/m<sup>2</sup> IV once per day on days 8 & 15
 
−
**For patients achieving CR or CRi, day 1 dose was reduced to 0.5 mg/m<sup>2</sup>
 
−
'''21-day cycle for 1 cycle, then 28-day cycle for up to 5 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MDACC 2009-0872:''' Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, York S, Ravandi F, Kwari M, Faderl S, Rios MB, Cortes J, Fayad L, Tarnai R, Wang SA, Champlin R, Advani A, O'Brien S. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012 Apr;13(4):403-11. Epub 2012 Feb 21. [https://doi.org/10.1016/S1470-2045(11)70386-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22357140 PubMed] NCT01134575
 
−
==Mitoxantrone, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone {{#subobject:910a81|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ecb2e4|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/10.1016/S0140-6736(10)62002-8 Parker et al. 2010 (CCLG ALL R3)]
 
−
|2003-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Idarubicin.2C_Asparaginase_Erwinia_chrysanthemi.2C_Vincristine.2C_Dexamethasone_88|Idarubicin, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
''Note: per the protocol, this regimen is intended only for patients 18 and younger. This regimen is for patients allergic to pegaspargase.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 20,000 units IM once per day on days 3, 5, 7, 9, 11, 13, 18, 20, 22, 24, 26, 28
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 3, 10, 17, 24
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> PO once per day on days 1 to 5, 15 to 19
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Age less than 2: 8 mg IT once per day on days 1 & 8
 
−
**Age 2: 10 mg IT once per day on days 1 & 8
 
−
**Age older than 2: 12 mg IT once per day on days 1 & 8
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''CCLG ALL R3:''' Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. [https://doi.org/10.1016/S0140-6736(10)62002-8 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21131038 PubMed] NCT00967057
 
−
==Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone {{#subobject:910a79|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e3cbe4|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/10.1016/S0140-6736(10)62002-8 Parker et al. 2010 (CCLG ALL R3)]
 
−
|2003-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Idarubicin.2C_Pegaspargase.2C_Vincristine.2C_Dexamethasone_88|Idarubicin, Pegaspargase, Vincristine, Dexamethasone]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
''Note: per the protocol, this regimen is intended only for patients 18 and younger.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Pegaspargase (Oncaspar)]] 1000 units/m<sup>2</sup> IM once per day on days 3 & 18
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 3, 10, 17, 24
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> PO once per day on days 1 to 5, 15 to 19
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**Age less than 2: 8 mg IT once per day on days 1 & 8
 
−
**Age 2: 10 mg IT once per day on days 1 & 8
 
−
**Age older than 2: 12 mg IT once per day on days 1 & 8
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*See paper for details of treatment beyond induction
 
−
</div></div>
 
−
===References===
 
−
#'''CCLG ALL R3:''' Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. [https://doi.org/10.1016/S0140-6736(10)62002-8 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21131038 PubMed] NCT00967057
 
−
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:60fc19|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058440/ Grupp et al. 2013 (Pedi CART19)]
 
−
|2011-NR
 
−
| style="background-color:#ffffbe" |Pilot
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267531/ Maude et al. 2014 (UPCC04409)]
 
−
|2012-2014
 
−
| style="background-color:#91cf61" |Phase 1/2a
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5996391/ Maude et al. 2018 (ELIANA)]
 
−
|2015-2017
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|ORR: 81%
 
−
|-
 
−
|}
 
−
''Note: dosing instructions are based on ELIANA.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Lymphodepleting therapy with [[Autologous_HSCT#FC|FC]] or [[Autologous_HSCT#CYVE|CYVE]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Tisagenlecleucel (Kymriah)]] by the following weight-based criteria:
 
−
**Up to 50 kg: 2 to 5 x 10<sup>6</sup> CTL019 transduced viable T-cells per kg body weight IV once on day 0
 
−
**Greater than 50 kg: 1.0 to 2.5 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
 
−
'''One course'''
 
−
</div></div>
 
−
===References===
 
−
#'''Pedi CART19:''' Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. Epub 2013 Mar 25. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. [https://doi.org/10.1056/NEJMoa1215134 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058440/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23527958 PubMed] NCT01626495
 
−
#'''UPCC04409:''' Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. [https://doi.org/10.1056/NEJMoa1407222 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267531/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25317870 PubMed] NCT01029366
 
−
#'''ELIANA:''' Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. [https://doi.org/10.1056/NEJMoa1709866 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1709866/suppl_file/nejmoa1709866_protocol.pdf link to supplementary protocol] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5996391/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29385370 PubMed] NCT02435849
 
−
=Consolidation after salvage therapy=
 
−
==Blinatumomab monotherapy {{#subobject:e7bh86|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1 cycle {{#subobject:2db26g|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/10.1001/jama.2021.0987 Locatelli et al. 2021 (Amgen 20120215)]
 
−
|2015-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Standard salvage consolidation chemotherapy
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Blinatumomab (Blincyto)]] 15 mcg/m<sup>2</sup>/day IV continuous infusion over 28 days, started on day 1 (total dose: 420 mcg/m<sup>2</sup>)
 
−
'''42-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic hematopoietic stem cell transplant]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 2 cycles {{#subobject:2db2g7|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/10.1001/jama.2021.0669 Brown et al. 2021 (COG AALL1331)]
 
−
|2014-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Standard salvage consolidation chemotherapy
 
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
−
|-
 
−
|}
 
−
''Note: insufficient dosing information was present in the abstract.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Blinatumomab (Blincyto)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Regimen_classes#Allogeneic_HSCT|Allogeneic hematopoietic stem cell transplant]]
 
−
</div></div>
 
−
===References===
 
−
#'''COG AALL1331:''' Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. [https://doi.org/10.1001/jama.2021.0669 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33651090/ PubMed] NCT02101853
 
−
#'''Amgen 20120215:''' Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Mergen N, Mohammad A, Kormany WN, Eckert C, Möricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. [https://doi.org/10.1001/jama.2021.0987 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33651091/ PubMed] NCT02393859
 
−
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9e6e8|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:1ba28d|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/NEJM198110083051502 Johnson et al. 1981]
 
−
|1976-1980
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198708203170801 Kersey et al. 1987]
 
−
|1982-1985
 
−
| style="background-color:#1a9851" |Quasi-randomized
 
−
|Auto HSCT
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|6ca28d}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. [https://doi.org/10.1056/NEJM198110083051502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7024804 PubMed]
 
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#Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. [https://doi.org/10.1056/NEJM198708203170801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3302708 PubMed]
 
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[[Category:B-cell acute lymphoblastic leukemia regimens]]
 
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[[Category:Disease-specific pages]]
 
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[[Category:Acute lymphoblastic leukemias]]
 
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[[Category:Pediatric hematologic neoplasms]]
 

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