Difference between revisions of "B-cell acute lymphoblastic leukemia, pediatric, Ph-positive"
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Warner-admin (talk | contribs) m (Text replacement - "=Guidelines=" to "=Guidelines= '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.'''") |
Warner-admin (talk | contribs) m (Text replacement - "==[https://www.nccn.org/ NCCN]==" to "==NCCN==") |
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<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> | <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= | + | {{TOC limit|limit=4}} |
=Guidelines= | =Guidelines= | ||
| − | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any | + | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' |
| − | == | + | ==NCCN== |
| − | *''NCCN does not have guidelines at this granular level; please see [https://www.nccn.org/ | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1496 NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia]''. |
| + | |||
| + | =Upfront therapy= | ||
| + | ==COG AALL1122 protocol {{#subobject:d3lac7|Regimen=1}}== | ||
| + | <div class="toccolours" style="background-color:#c8a2c8"> | ||
| + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
| + | !style="width: 33%"|Study | ||
| + | !style="width: 33%"|Dates of enrollment | ||
| + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
| + | |- | ||
| + | |[https://doi.org/10.1016/s2352-3026(23)00088-1 Hunger et al. 2023 (COG AALL1122)] | ||
| + | |2012-03-13 to 2014-05-27 | ||
| + | | style="background-color:#91cf61" |Phase 2 (RT) | ||
| + | |- | ||
| + | |} | ||
| + | <div class="toccolours" style="background-color:#eeeeee"> | ||
| + | ===Induction, 1A {{#subobject:f3nchf|Variant=1}}=== | ||
| + | ''Note: Per the protocol, "All patients will receive Induction 1A as per institutional standard of care." Only the details for dasatinib are provided.'' | ||
| + | <div class="toccolours" style="background-color:#b3e2cd"> | ||
| + | ====Targeted therapy==== | ||
| + | *[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> PO once per day on days 15 to 33 | ||
| + | '''33-day course, followed immediately by:''' | ||
| + | </div></div><br> | ||
| + | <div class="toccolours" style="background-color:#eeeeee"> | ||
| + | ===Induction, 1B=== | ||
| + | <div class="toccolours" style="background-color:#b3e2cd"> | ||
| + | ====Chemotherapy==== | ||
| + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 28 | ||
| + | *[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 28 | ||
| + | *[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 3 to 6, 10 to 13, 17 to 20, 24 to 27 | ||
| + | ====Targeted therapy==== | ||
| + | *[[Dasatinib (Sprycel)]] 60 mg/m<sup>2</sup> PO once per day | ||
| + | ====CNS therapy, prophylaxis==== | ||
| + | *[[Methotrexate (MTX)]] IT once per day on days 3 & 17 | ||
| + | '''6- to 8-week course, including 2 to 4 weeks of recovery period, followed by: | ||
| + | </div></div><br> | ||
| + | <div class="toccolours" style="background-color:#eeeeee"> | ||
| + | ===Consolidation, Block 1=== | ||
| + | <div class="toccolours" style="background-color:#b3e2cd"> | ||
| + | ====Chemotherapy==== | ||
| + | To be completed | ||
| + | </div></div></div> | ||
| + | ===References=== | ||
| + | # '''COG AALL1122:''' Hunger SP, Tran TH, Saha V, Devidas M, Valsecchi MG, Gastier-Foster JM, Cazzaniga G, Reshmi SC, Borowitz MJ, Moorman AV, Heerema NA, Carroll AJ, Martin-Regueira P, Loh ML, Raetz EA, Schultz KR, Slayton WB, Cario G, Schrappe M, Silverman LB, Biondi A. Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2023 Jul;10(7):e510-e520. [https://doi.org/10.1016/s2352-3026(23)00088-1 link to original article] '''contains partial dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/37407142/ PubMed] [https://clinicaltrials.gov/study/NCT01460160 NCT01460160] | ||
=Upfront induction therapy= | =Upfront induction therapy= | ||
| Line 34: | Line 77: | ||
|- | |- | ||
|} | |} | ||
| + | ''Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of dasatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.'' | ||
| + | <div class="toccolours" style="background-color:#cbd5e7"> | ||
| + | ====Preceding treatment==== | ||
| + | *[[#Dexamethasone_monotherapy|Dexamethasone]] pre-phase | ||
| + | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| − | *[[Daunorubicin (Cerubidine)]] | + | *[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 5 & 12 |
| − | *[[Pegaspargase (Oncaspar)]] | + | *[[Pegaspargase (Oncaspar)]] 2000 units/m<sup>2</sup> IM once per day on days 6 & 26 |
| − | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26 |
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
| − | *[[Prednisone (Sterapred)]] | + | *[[Prednisone (Sterapred)]] 15 mg/m<sup>2</sup> PO three times per day on days 5 to 28 |
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Dasatinib (Sprycel)]] 80 mg/m<sup>2</sup>/day PO | *[[Dasatinib (Sprycel)]] 80 mg/m<sup>2</sup>/day PO | ||
| Line 47: | Line 95: | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
| − | * | + | *Induction II; see paper for details |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | # '''CCCG-ALL-2015-Ph:''' Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. [https://doi.org/10.1001/jamaoncol.2019.5868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31944221/ PubMed] ChiCTR-IPR-14005706 | + | # '''CCCG-ALL-2015-Ph:''' Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. [https://doi.org/10.1001/jamaoncol.2019.5868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31944221/ PubMed] ChiCTR-IPR-14005706 |
| − | + | ||
==Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib {{#subobject:d3yhc7|Regimen=1}}== | ==Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib {{#subobject:d3yhc7|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
| Line 69: | Line 117: | ||
|- | |- | ||
|} | |} | ||
| + | ''Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of imatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.'' | ||
| + | <div class="toccolours" style="background-color:#cbd5e7"> | ||
| + | ====Preceding treatment==== | ||
| + | *[[#Dexamethasone_monotherapy|Dexamethasone]] pre-phase | ||
| + | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| − | *[[Daunorubicin (Cerubidine)]] | + | *[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 5 & 12 |
| − | *[[Pegaspargase (Oncaspar)]] | + | *[[Pegaspargase (Oncaspar)]] 2000 units/m<sup>2</sup> IM once per day on days 6 & 26 |
| − | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26 |
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
| − | *[[Prednisone (Sterapred)]] | + | *[[Prednisone (Sterapred)]] 15 mg/m<sup>2</sup> PO three times per day on days 5 to 28 |
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Imatinib (Gleevec)]] 300 mg/m<sup>2</sup>/day PO | *[[Imatinib (Gleevec)]] 300 mg/m<sup>2</sup>/day PO | ||
| Line 82: | Line 135: | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
| − | * | + | *Induction II; see paper for details |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | # '''CCCG-ALL-2015-Ph:''' Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. [https://doi.org/10.1001/jamaoncol.2019.5868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31944221/ PubMed] ChiCTR-IPR-14005706 | + | # '''CCCG-ALL-2015-Ph:''' Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. [https://doi.org/10.1001/jamaoncol.2019.5868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31944221/ PubMed] ChiCTR-IPR-14005706 |
| + | |||
| + | =Upfront induction therapy= | ||
| + | ==Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib {{#subobject:d3ob07|Regimen=1}}== | ||
| + | <div class="toccolours" style="background-color:#eeeeee"> | ||
| + | ===Regimen {{#subobject:f30uhf|Variant=1}}=== | ||
| + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
| + | !style="width: 20%"|Study | ||
| + | !style="width: 20%"|Dates 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/PMC6990720/ Shen et al. 2020 (CCCG-ALL-2015-Ph)] | ||
| + | |2015-2018 | ||
| + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
| + | |[[#Daunorubicin.2C_Pegaspargase.2C_Vincristine.2C_Prednisone.2C_Imatinib|Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib]] | ||
| + | | style="background-color:#1a9850" |Superior EFS (primary endpoint) | ||
| + | |- | ||
| + | |} | ||
| + | ''Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of dasatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.'' | ||
| + | <div class="toccolours" style="background-color:#cbd5e7"> | ||
| + | ====Preceding treatment==== | ||
| + | *[[#Dexamethasone_monotherapy|Dexamethasone]] pre-phase | ||
| + | </div> | ||
| + | <div class="toccolours" style="background-color:#b3e2cd"> | ||
| + | ====Chemotherapy==== | ||
| + | *[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 5 & 12 | ||
| + | *[[Pegaspargase (Oncaspar)]] 2000 units/m<sup>2</sup> IM once per day on days 6 & 26 | ||
| + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26 | ||
| + | ====Glucocorticoid therapy==== | ||
| + | *[[Prednisone (Sterapred)]] 15 mg/m<sup>2</sup> PO three times per day on days 5 to 28 | ||
| + | ====Targeted therapy==== | ||
| + | *[[Dasatinib (Sprycel)]] 80 mg/m<sup>2</sup>/day PO | ||
| + | '''28-day course''' | ||
| + | </div> | ||
| + | <div class="toccolours" style="background-color:#cbd5e7"> | ||
| + | ====Subsequent treatment==== | ||
| + | *Induction II; see paper for details | ||
| + | </div></div> | ||
| + | ===References=== | ||
| + | # '''CCCG-ALL-2015-Ph:''' Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. [https://doi.org/10.1001/jamaoncol.2019.5868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31944221/ PubMed] ChiCTR-IPR-14005706 | ||
| + | |||
| + | ==Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib {{#subobject:d3yhc7|Regimen=1}}== | ||
| + | <div class="toccolours" style="background-color:#eeeeee"> | ||
| + | ===Regimen {{#subobject:f3e30f|Variant=1}}=== | ||
| + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
| + | !style="width: 20%"|Study | ||
| + | !style="width: 20%"|Dates 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/PMC6990720/ Shen et al. 2020 (CCCG-ALL-2015-Ph)] | ||
| + | |2015-2018 | ||
| + | | style="background-color:#1a9851" |Phase 3 (C) | ||
| + | |[[#Daunorubicin.2C_Pegaspargase.2C_Vincristine.2C_Prednisone.2C_Dasatinib|Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib]] | ||
| + | | style="background-color:#d73027" |Inferior EFS | ||
| + | |- | ||
| + | |} | ||
| + | ''Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of imatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.'' | ||
| + | <div class="toccolours" style="background-color:#cbd5e7"> | ||
| + | ====Preceding treatment==== | ||
| + | *[[#Dexamethasone_monotherapy|Dexamethasone]] pre-phase | ||
| + | </div> | ||
| + | <div class="toccolours" style="background-color:#b3e2cd"> | ||
| + | ====Chemotherapy==== | ||
| + | *[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 5 & 12 | ||
| + | *[[Pegaspargase (Oncaspar)]] 2000 units/m<sup>2</sup> IM once per day on days 6 & 26 | ||
| + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26 | ||
| + | ====Glucocorticoid therapy==== | ||
| + | *[[Prednisone (Sterapred)]] 15 mg/m<sup>2</sup> PO three times per day on days 5 to 28 | ||
| + | ====Targeted therapy==== | ||
| + | *[[Imatinib (Gleevec)]] 300 mg/m<sup>2</sup>/day PO | ||
| + | '''28-day course''' | ||
| + | </div> | ||
| + | <div class="toccolours" style="background-color:#cbd5e7"> | ||
| + | ====Subsequent treatment==== | ||
| + | *Induction II; see paper for details | ||
| + | </div></div> | ||
| + | ===References=== | ||
| + | # '''CCCG-ALL-2015-Ph:''' Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. [https://doi.org/10.1001/jamaoncol.2019.5868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31944221/ PubMed] ChiCTR-IPR-14005706 | ||
| + | |||
=Consolidation after upfront therapy (including post-remission therapy)= | =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.'' | ''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.'' | ||
| Line 142: | Line 277: | ||
|} | |} | ||
''<sup>1</sup>This regimen did not meet the primary efficacy endpoint in the ITT population, but there was a possible signal in the as-treated population.''<br> | ''<sup>1</sup>This regimen did not meet the primary efficacy endpoint in the ITT population, but there was a possible signal in the as-treated population.''<br> | ||
| − | |||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
| − | * Berlin–Frankfurt–Munster high-risk backbone | + | * Berlin–Frankfurt–Munster high-risk backbone induction |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
| − | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 28 |
| − | *[[Mercaptopurine (6-MP)]] | + | *[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 28 |
| − | *[[Cytarabine (Ara-C)]] | + | *[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 3 to 6, 10 to 13, 17 to 20, 24 to 27 |
====Targeted therapy==== | ====Targeted therapy==== | ||
| − | *[[Imatinib (Gleevec)]] | + | *[[Imatinib (Gleevec)]] 300 mg/m<sup>2</sup> PO once per day on days 1 to 28 |
====CNS therapy, prophylaxis==== | ====CNS therapy, prophylaxis==== | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
| + | '''28-day course''' | ||
| + | </div> | ||
| + | <div class="toccolours" style="background-color:#cbd5e8"> | ||
| + | ====Subsequent treatment==== | ||
| + | *Consolidation block HR1 (see paper for details) | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | # '''EsPhALL:''' Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Aricò M, Röttgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. Epub 2012 Aug 14. [https://doi.org/10.1016/S1470-2045(12)70377-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431502/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22898679/ PubMed] [https://clinicaltrials.gov/study/NCT00287105 NCT00287105] | + | # '''EsPhALL:''' Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Aricò M, Röttgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. Epub 2012 Aug 14. [https://doi.org/10.1016/S1470-2045(12)70377-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431502/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22898679/ PubMed] [https://clinicaltrials.gov/study/NCT00287105 NCT00287105] |
[[Category:B-cell acute lymphoblastic leukemia regimens]] | [[Category:B-cell acute lymphoblastic leukemia regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Acute lymphoblastic leukemias]] | [[Category:Acute lymphoblastic leukemias]] | ||
[[Category:Pediatric hematologic neoplasms]] | [[Category:Pediatric hematologic neoplasms]] | ||
Latest revision as of 11:39, 13 May 2024
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David Noyd, MD, MPH University of Washington Seattle, WA, USA |
This page contains studies that were specific to pediatric populations. For the more general pediatric B-ALL page, follow this link. For the more general Ph+ B-ALL page, follow this link.
5 regimens on this page
5 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia.
Upfront therapy
COG AALL1122 protocol
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Hunger et al. 2023 (COG AALL1122) | 2012-03-13 to 2014-05-27 | Phase 2 (RT) |
Induction, 1A
Note: Per the protocol, "All patients will receive Induction 1A as per institutional standard of care." Only the details for dasatinib are provided.
Targeted therapy
- Dasatinib (Sprycel) 60 mg/m2 PO once per day on days 15 to 33
33-day course, followed immediately by:
Induction, 1B
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 1 & 28
- Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 1 to 28
- Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 3 to 6, 10 to 13, 17 to 20, 24 to 27
Targeted therapy
- Dasatinib (Sprycel) 60 mg/m2 PO once per day
CNS therapy, prophylaxis
- Methotrexate (MTX) IT once per day on days 3 & 17
6- to 8-week course, including 2 to 4 weeks of recovery period, followed by:
Consolidation, Block 1
Chemotherapy
To be completed
References
- COG AALL1122: Hunger SP, Tran TH, Saha V, Devidas M, Valsecchi MG, Gastier-Foster JM, Cazzaniga G, Reshmi SC, Borowitz MJ, Moorman AV, Heerema NA, Carroll AJ, Martin-Regueira P, Loh ML, Raetz EA, Schultz KR, Slayton WB, Cario G, Schrappe M, Silverman LB, Biondi A. Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2023 Jul;10(7):e510-e520. link to original article contains partial dosing details in supplement PubMed NCT01460160
Upfront induction therapy
Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Shen et al. 2020 (CCCG-ALL-2015-Ph) | 2015-2018 | Phase 3 (E-switch-ic) | Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib | Superior EFS (primary endpoint) |
Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of dasatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.
Preceding treatment
- Dexamethasone pre-phase
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 5 & 12
- Pegaspargase (Oncaspar) 2000 units/m2 IM once per day on days 6 & 26
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26
Glucocorticoid therapy
- Prednisone (Sterapred) 15 mg/m2 PO three times per day on days 5 to 28
Targeted therapy
- Dasatinib (Sprycel) 80 mg/m2/day PO
28-day course
Subsequent treatment
- Induction II; see paper for details
References
- CCCG-ALL-2015-Ph: Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. link to original article link to PMC article contains dosing details in supplement PubMed ChiCTR-IPR-14005706
Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Shen et al. 2020 (CCCG-ALL-2015-Ph) | 2015-2018 | Phase 3 (C) | Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib | Inferior EFS |
Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of imatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.
Preceding treatment
- Dexamethasone pre-phase
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 5 & 12
- Pegaspargase (Oncaspar) 2000 units/m2 IM once per day on days 6 & 26
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26
Glucocorticoid therapy
- Prednisone (Sterapred) 15 mg/m2 PO three times per day on days 5 to 28
Targeted therapy
- Imatinib (Gleevec) 300 mg/m2/day PO
28-day course
Subsequent treatment
- Induction II; see paper for details
References
- CCCG-ALL-2015-Ph: Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. link to original article link to PMC article contains dosing details in supplement PubMed ChiCTR-IPR-14005706
Upfront induction therapy
Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Shen et al. 2020 (CCCG-ALL-2015-Ph) | 2015-2018 | Phase 3 (E-switch-ic) | Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib | Superior EFS (primary endpoint) |
Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of dasatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.
Preceding treatment
- Dexamethasone pre-phase
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 5 & 12
- Pegaspargase (Oncaspar) 2000 units/m2 IM once per day on days 6 & 26
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26
Glucocorticoid therapy
- Prednisone (Sterapred) 15 mg/m2 PO three times per day on days 5 to 28
Targeted therapy
- Dasatinib (Sprycel) 80 mg/m2/day PO
28-day course
Subsequent treatment
- Induction II; see paper for details
References
- CCCG-ALL-2015-Ph: Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. link to original article link to PMC article contains dosing details in supplement PubMed ChiCTR-IPR-14005706
Daunorubicin, Pegaspargase, Vincristine, Prednisone, Imatinib
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Shen et al. 2020 (CCCG-ALL-2015-Ph) | 2015-2018 | Phase 3 (C) | Daunorubicin, Pegaspargase, Vincristine, Prednisone, Dasatinib | Inferior EFS |
Note: The schedule as reported begins after the 4-day pre-phase was completed; the exact start day of imatinib was not specified. Pegaspargase was specified as being given for 1 dose, but also specified to be given on 2 days during induction.
Preceding treatment
- Dexamethasone pre-phase
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 5 & 12
- Pegaspargase (Oncaspar) 2000 units/m2 IM once per day on days 6 & 26
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 5, 12, 19, 26
Glucocorticoid therapy
- Prednisone (Sterapred) 15 mg/m2 PO three times per day on days 5 to 28
Targeted therapy
- Imatinib (Gleevec) 300 mg/m2/day PO
28-day course
Subsequent treatment
- Induction II; see paper for details
References
- CCCG-ALL-2015-Ph: Shen S, Chen X, Cai J, Yu J, Gao J, Hu S, Zhai X, Liang C, Ju X, Jiang H, Jin R, Wu X, Wang N, Tian X, Pan K, Jiang H, Sun L, Fang Y, Li CK, Hu Q, Yang M, Zhu Y, Zhang H, Li C, Pei D, Jeha S, Yang JJ, Cheng C, Tang J, Zhu X, Pui CH. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):358-366. Epub 2020 Jan 16. link to original article link to PMC article contains dosing details in supplement PubMed ChiCTR-IPR-14005706
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.
Etoposide, Ifosfamide, Imatinib
Regimen
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Schultz et al. 2009 (COG AALL0031) | 2002-2006 | Phase 2 (RT) |
Note: the schedule is not specified for etoposide and ifosfamide, and the filgrastim dose is erroneous within the manuscript.
Preceding treatment
- Induction (see paper for details)
Chemotherapy
- Etoposide (Vepesid) 100 mg/m2 IV (schedule not specified)
- Ifosfamide (Ifex) 3400 mg/m2 IV (schedule not specified)
Targeted therapy
- Imatinib (Gleevec) 340 mg/m2 PO once per day
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 6 to 15
21-day course
Subsequent treatment
- Consolidation block 2 (see paper for details)
References
- COG AALL0031: Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, Wang C, Davies SM, Gaynon PS, Trigg M, Rutledge R, Burden L, Jorstad D, Carroll A, Heerema NA, Winick N, Borowitz MJ, Hunger SP, Carroll WL, Camitta B. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a Children's Oncology Group study. J Clin Oncol. 2009 Nov 1;27(31):5175-81. Epub 2009 Oct 5. link to original article link to PMC article PubMed NCT00022737
- Update: Schultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, Zheng HW, Davies SM, Gaynon PS, Trigg M, Rutledge R, Jorstad D, Winick N, Borowitz MJ, Hunger SP, Carroll WL, Camitta B; Children’s Oncology Group. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031. Leukemia. 2014 Jul;28(7):1467-71. Epub 2014 Jan 20. link to original article link to PMC article PubMed
Imatinib-based consolidation
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Biondi et al. 2012 (EsPhALL) | 2004-2009 | Phase 3 (E-esc) | No imatinib in consolidation | Did not meet primary endpoint of DFS481 |
1This regimen did not meet the primary efficacy endpoint in the ITT population, but there was a possible signal in the as-treated population.
Preceding treatment
- Berlin–Frankfurt–Munster high-risk backbone induction
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 1 & 28
- Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 1 to 28
- Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 3 to 6, 10 to 13, 17 to 20, 24 to 27
Targeted therapy
- Imatinib (Gleevec) 300 mg/m2 PO once per day on days 1 to 28
CNS therapy, prophylaxis
28-day course
Subsequent treatment
- Consolidation block HR1 (see paper for details)
References
- EsPhALL: Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, Pieters R, Stary J, Escherich G, Campbell M, Li CK, Vora A, Aricò M, Röttgers S, Saha V, Valsecchi MG. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012 Sep;13(9):936-45. Epub 2012 Aug 14. link to original article link to PMC article contains dosing details in supplement PubMed NCT00287105