Difference between revisions of "B-cell acute lymphoblastic leukemia, pediatric"
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DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisone | 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 | <br>DVPA: '''<u>D</u>'''aunorubicin, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone, '''<u>A</u>'''sparaginase | ||
− | ===Regimen variant #1, 25 | + | ===Regimen variant #1, 25/1.5/6000/60 {{#subobject:3fe1a2|Variant=1}}=== |
{| class="wikitable" style="width: 40%; text-align:center;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
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*Standard versus increased intensity post-remission therapy (see paper for details) | *Standard versus increased intensity post-remission therapy (see paper for details) | ||
− | ===Regimen variant #2, 30 | + | ===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" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !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)] | |[http://www.bloodjournal.org/content/111/9/4477.long Möricke et al. 2008 (ALL-BFM 95)] | ||
+ | |1995-2000 | ||
| style="background-color:#91cf61" |Non-randomized | | 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 | + | ''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.'' |
====Chemotherapy==== | ====Chemotherapy==== | ||
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*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) 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)]] 5000 units IV over 60 minutes once per day on days 12, 15, 18, 21, 24, 27, 30, 33 | *[[Asparaginase (Elspar)]] 5000 units IV over 60 minutes once per day on days 12, 15, 18, 21, 24, 27, 30, 33 | ||
− | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28 | + | *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28, tapered over 9 days |
====CNS therapy==== | ====CNS therapy==== | ||
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====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *See | + | *See papers for details |
− | ===Regimen variant #3, 30/10,000 | + | ===Regimen variant #3, 30/1.5/10,000/60 ("Protocol I") {{#subobject:0ccc82|Variant=1}}=== |
{| class="wikitable" style="width: 40%; text-align:center;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
Line 2,089: | Line 2,095: | ||
*See papers for details | *See papers for details | ||
− | ===Regimen variant #4, 40/10,000 | + | ===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;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
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#'''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 verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/18285545 PubMed] | #'''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 verified protocol''' [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] | ##'''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] | ||
+ | #'''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 verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/24344215/ PubMed] NCT00764907 | ||
==DOLP (Prednisolone) {{#subobject:3c7jg7|Regimen=1}}== | ==DOLP (Prednisolone) {{#subobject:3c7jg7|Regimen=1}}== |
Revision as of 12:58, 17 October 2021
Section editor transclusions 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 this link.
34 regimens on this page
40 variants on this page
|
Guidelines
"How I Treat"
- 2020: Hunger & Raetz. How I treat relapsed acute lymphoblastic leukemia in the pediatric population
NCCN
COG AALL0932
For Standard Risk B-ALL
Induction
Pegaspargase, Vincristine, Dexamethasone
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Maloney et al. 2019 (COG AALL0331) | 2005-2010 | Non-randomized portion of RCT |
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Note: there are very minor differences in timing between protocols; see papers for details.
Chemotherapy
- Pegaspargase (Oncaspar) 2,500 units/m2 IV once over 1 - 2 hours on day 4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
- Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 28
CNS prophylaxis
- Cytarabine (Ara-C) IT once on day 0
Age | 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.
Age | 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
Age | 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/m2 x 2 doses PO given 48 and 60 hours after the lumbar puncture on days 10-11 and 31-32
35-day course
Subsequent treatment
- COG AALL0331, M2 marrow or M1 marrow with MRD of at least 1% at day 29: Extended induction
- COG AALL0932: 6-MP & Vincristine consolidation
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. link to original article link to PMC article contains verified protocol 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. link to original article contains verified protocol PubMed NCT01190930
Consolidation
For AR B-ALL patients, LR-C Arm, and B-LLy
Mercaptopurine & Vincristine
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Mercaptopurine (6-MP) 75 mg/m2/day PO on days 1 to 28
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once on day 1
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15
Age | 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/m2 x 2 doses PO given 48 and 60 hours after the lumbar puncture on days 3-4, 10-11, and 17-18.
28-day course
Subsequent treatment
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. link to original article contains verified protocol PubMed NCT01190930
Interim Maintenance I
For AR B-ALL patients, LR-C Arm, and B-LLy
Methotrexate & Vincristine
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Matloub et al. 2011 (COG CCG-1991) | 2000-2005 | Phase III (E-de-esc) | Mercaptopurine, MTX, Vincristine, Dexamethasone | Superior EFS |
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
- COG AALL0932: 6-MP & Vincristine consolidation
Chemotherapy
- Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
- Given over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted).
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
CNS prophylaxis
- Methotrexate (MTX) IT once on day 31
Age | 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/m2 x 2 doses given 48 and 60 hours after the lumbar puncture on days 33-34
8-week course
Subsequent treatment
- COG AALL0932: AALL0932 delayed intensification
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Delayed Intensification
For AR B-ALL patients, LR-C Arm, and B-LLy
AALL0932 delayed intensification
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on day 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 to 32, 36 to 39
- Doxorubicin (Adriamycin) 25 mg/m2 IV push/infusion over 1 - 15 minutes once per day on days 1, 8, 15
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 - 2 hours once on day 4
- Thioguanine (Tabloid) 60 mg/m2/day PO once per day on days 29 to 42
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Dexamethasone (Decadron) 5 mg/m2/dose PO twice daily on days 1 to 7, 15 to 21 (10 mg/m2/day)
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 & 29
Age | 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/m2 x 2 doses given 48 and 60 hours after the lumbar puncture on days 3-4 and 31-32.
8-week course
Subsequent treatment
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. link to original article contains verified protocol PubMed NCT01190930
Interim Maintenance II
For AR B-ALL patients, LR-C Arm, and B-LLy
Methotrexate & Vincristine
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Matloub et al. 2011 (COG CCG-1991) | 2000-2005 | Phase III (E-de-esc) | Mercaptopurine, MTX, Vincristine, Dexamethasone | Superior EFS |
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
- COG AALL0932: 6-MP & Vincristine consolidation
Chemotherapy
- Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
- Given over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted).
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
CNS prophylaxis
- Methotrexate (MTX) IT once on day 31
Age | 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/m2 x 2 doses given 48 and 60 hours after the lumbar puncture on days 3-4 and 33-34.
8-week course
Subsequent treatment
- COG AALL0932: AALL0932 delayed intensification
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Maintenance Arm A and C
For AR B-ALL patients, and LR-C Arm
Vincristine/Dexamethasone Pulses
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Randomized portion of RCT |
Preceding treatment
- COG AALL0932: MTX & Vincristine interim maintenance
Chemotherapy
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 to 5, 29 - 33, and 578 - 61 (6 mg/m2/day)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 to 84
CNS prophylaxis
- Methotrexate (MTX) IT once on day 1
Age | 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
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Maintenance Arm B and D
Vincristine/Dexamethasone Pulses
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Randomized portion of RCT |
Preceding treatment
- COG AALL0932: MTX & Vincristine interim maintenance
Chemotherapy
- Currently maintenance arm B and D are also treated with Methotrexate (MTX) PO at 20 mg/m2 (decreased from the starting dose of 40 mg/m2) on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 to 5, 29 - 33, and 57 - 61 (6 mg/m2/day)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 to 84
CNS prophylaxis
- Methotrexate (MTX) IT once on day 1
Age | 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
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Maintenance Arm DS
For DS AR B-ALL patients and DS B-LLy
Vincristine/Dexamethasone
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Randomized portion of RCT |
Preceding treatment
- COG AALL0932: MTX & Vincristine interim maintenance
Chemotherapy
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1
- Dexamethasone (Decadron) 3 mg/m2/dose IV or PO twice daily on days 1 to 5 (6 mg/m2/day) (DO NOT TAPER)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 to 84
CNS prophylaxis
- Methotrexate (MTX) IT once on day 1
Age | 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
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Arm LR-M
Consolidation
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Randomized portion of RCT |
Chemotherapy
- Methotrexate (MTX) IV at 1,000 mg/m2 on days 8, 29, 50, 71, 92, and 113.
Given as a 200 mg/m2 bolus over 20 - 30 minutes followed by 800 mg/m2 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/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 78, and 85.
- Dexamethasone (Decadron) 3 mg/m2/dose IV or PO twice daily on days 15 - 21, and 78 - 84. (6 mg/m2/day)
- Mercaptopurine (6-MP) 50 mg/m2/dose PO once per day on days 1 to 33
- Folinic acid (Leucovorin) 10 mg/m2 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, and 114 - 115.
CNS prophylaxis
- Methotrexate (MTX) IT once on day 8, 29, 50, 71, 92, and 113 (To be delivered within 6 hours of the beginning of the IV methotrexate infusion, -6hr to + 6 hr)
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
19-week cycle
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Maintenance
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Randomized portion of RCT |
Chemotherapy
Methotrexate (MTX) DATES CHANGE DEPENDING ON CYCLE NUMBER
Cycles 1 and 4:
- Methotrexate (MTX) PO at 20 mg/m2 on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 92, 99, and 106.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 and 8.
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 - 7. (6 mg/m2/day, do not taper)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 112. (NOTE: Higher 6-MP dose than in consolidation)
Cycles 2 and 5:
- Methotrexate (MTX) PO at 20 mg/m2 on days 1, 8, 15, 22, 29, 36, 43, 50, 64, 71, 78, 85, 92, 99, and 106.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 and 8.
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 - 7. (6 mg/m2/day, do not taper)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 112. (NOTE: Higher 6-MP dose than in consolidation)
Cycles 3 and 6:
- Methotrexate (MTX) PO at 20 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, and 106.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 and 8.
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 - 7. (6 mg/m2/day, do not taper)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 112. (NOTE: Higher 6-MP dose than in consolidation)
Cycle 7:
- Methotrexate (MTX) PO at 20 mg/m2 on days 1, 8, 15, 29, 22, 36, 43, 50, 57, and 64
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 and 8.
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 - 7. (6 mg/m2/day, do not taper)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 70. (NOTE: Higher 6-MP dose than in consolidation)
CNS prophylaxis
DATES CHANGE DEPENDING ON CYCLE NUMBER
Cycles 1 and 4:
- Methotrexate (MTX) IT once on day 1 and 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
Age | 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.
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Maintenance Arm LLy
Vincristine/Dexamethasone
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Randomized portion of RCT |
Preceding treatment
- COG AALL0932: MTX & Vincristine interim maintenance
Chemotherapy
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57. (4 Week Intervals)
- Dexamethasone (Decadron) 3 mg/m2/dose PO twice daily on days 1 - 5, 29 - 33, and 57 - 61. (6 mg/m2/day) (DO NOT TAPER)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 to 84.
CNS prophylaxis
- Methotrexate (MTX) IT once on day 1
Age | 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
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
AALL1131
Induction
Daunorubicin, Pegaspargase, Vincristine, Dexamethasone
back to top |
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | 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.
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on day 4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
Patients < 10 years ONLY:
- Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 14
Patients ≥ 10 years ONLY:
- Prednisone (Sterapred) 30 mg/m2/dose PO twice per day on days 1 to 28
CNS prophylaxis
- Cytarabine (Ara-C) as follows:
- 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) as follows:
- 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) as follows: (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
Subsequent treatment
- See protocol for details of treatment beyond induction
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. link to original article link to PMC article PubMed NCT02883049
HR B-ALL
Consolidation
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on days 1 and 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, 36 - 39.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 - 2 hours once on days 15, and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.
- Mercaptopurine (6-MP) 60 mg/m2/dose PO once per day on days 1 - 14, and 29 - 42.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15, and 22.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day Course
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. link to original article link to PMC article PubMed NCT02883049
- 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. link to original article contains verified protocol PubMed NCT01190930
Interim Maintenance with HD MTX
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.
- Mercaptopurine (6-MP) 25 mg/m2/dose PO once per day on days 1 - 56.
- High Dose Methotrexate (MTX) 5,000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
- Methotrexate 500 mg/m2 IV infused over 30 minutes. This is followed, immediately, by methotrexate 4,500 mg/m2 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/m2 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 - 4, 17 - 18, 31 - 32, and 45 - 46.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 and 29.
Age | 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
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. link to original article link to PMC article PubMed NCT02883049
- 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. link to original article contains verified protocol PubMed NCT01190930
Delayed Intensification
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV push over 1 to 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on days 4 and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 - 7 and 15 - 21.
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on day 29 ONLY.
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.
- Thioguanine (Tabloid) 60 mg/m2/day PO once per day on days 29 to 42.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 29, and 36.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article link to PMC article PubMed NCT02883049
Maintenance HR B-ALL
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
Cycles 1-4
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 84.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, 36, 43, 50, 57, 64, 71 and 78.
- Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.
Cycles 5 and Later
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 84.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.
- Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.
CNS prophylaxis
Cycles 1-4
- Methotrexate (MTX) IT once per day on days 1 and 29.
Cycles 5 and Later
- Methotrexate (MTX) IT once per day on day 1.
Age | 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.
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. link to original article link to PMC article PubMed NCT02883049
VHR B-ALL
Consolidation
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on day 15 and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on day 1 and 29.
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, and 36 - 39.
- Mercaptopurine (6-MP) 60 mg/m2/dose PO once per day on days 1 - 14 and 29 - 42.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15, and 22. (Omit days 15 and 22 for CNS3 Patients)
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article link to PMC article PubMed NCT02883049
Interim Maintenance I with HD MTX
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.
- Mercaptopurine (6-MP) 60 mg/m2/dose PO once per day on days 1 - 56.
- High Dose Methotrexate (MTX) 5,000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
- Methotrexate 500 mg/m2 IV infused over 30 minutes. This is followed, immediately, by methotrexate 4,500 mg/m2 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/m2 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 - 4, 17 - 18, 31 - 32, and 45 - 46.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 and 29.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
28-Day course
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. link to original article link to PMC article PubMed NCT02883049
Delayed Intensification
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV push over 1 to 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on day 4 and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 - 7 and 15 - 21.
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on day 29 ONLY.
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.
- Thioguanine (Tabloid) 60 mg/m2/day PO once per day on days 29 to 42.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on day 1, 29, and 36.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article link to PMC article PubMed NCT02883049
Interim Maintenance II with Capizzi MTX
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, and 41.
- Methotrexate (MTX) 100 mg/m2 IV over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted) on days 1, 150 mg/m2 on day 11, 200 mg/m2 on day 21, 250 mg/m2 on day 31, and 300 mg/m2 on day 41.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on day 2 and 22.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 and 31.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article link to PMC article PubMed NCT02883049
VHR Arm Maintenance
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Radiotherapy
For Patients with CNS3 Disease
- Total body irradiation (TBI) 1,800 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/m2/dose PO once per day on days 1 - 84.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).
- Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.
CNS 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).
Age | 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.
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. link to original article link to PMC article PubMed NCT02883049
Ph-Like B-ALL (Dasatinib Arm)
Consolidation (Dasatinib Arm)
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on days 1 and 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, 36 - 39.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 - 2 hours once on days 15, and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.
- Mercaptopurine (6-MP) 60 mg/m2/dose PO once per day on days 1 - 14, and 29 - 42.
- Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15, and 22.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
- Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.
56-Day Course
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. link to original article link to PMC article PubMed NCT02883049
- 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. link to original article contains verified protocol PubMed NCT01190930
Interim Maintenance with HD MTX (Dasatinib Arm)
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.
- Mercaptopurine (6-MP) 25 mg/m2/dose PO once per day on days 1 - 56.
- High Dose Methotrexate (MTX) 5,000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
- Methotrexate 500 mg/m2 IV infused over 30 minutes. This is followed, immediately, by methotrexate 4,500 mg/m2 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/m2 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 - 4, 17 - 18, 31 - 32, and 45 - 46.
- Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 63.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 and 29.
Age | 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
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. link to original article link to PMC article PubMed NCT02883049
- 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. link to original article contains verified protocol PubMed NCT01190930
Delayed Intensification (Dasatinib Arm)
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV push over 1 to 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on days 4 and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 - 7 and 15 - 21.
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on day 29 ONLY.
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.
- Thioguanine (Tabloid) 60 mg/m2/day PO once per day on days 29 to 42.
- Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 29, and 36.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article
Interim Maintenance II with Capizzi MTX (Dasatinib Arm)
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, and 41.
- Methotrexate (MTX) 100 mg/m2 IV over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted) on days 1, 150 mg/m2 on day 11, 200 mg/m2 on day 21, 250 mg/m2 on day 31, and 300 mg/m2 on day 41.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on day 2 and 22.
- Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 and 31.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article link to PMC article PubMed NCT02883049
Maintenance (Dasatinib Arm)
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Radiotherapy
For Patients with CNS3 Disease
- Total body irradiation (TBI) 1,800 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/m2/dose PO once per day on days 1 - 84.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).
- Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.
- Dasatinib (Sprycel) 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 84.
CNS 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).
Age | 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.
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. link to original article link to PMC article PubMed NCT02883049
DS HR B-ALL
Induction
Daunorubicin, Pegaspargase, Vincristine, Dexamethasone
back to top |
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | 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.
Chemotherapy
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on day 4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, and 22
Patients < 10 years ONLY:
- Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 28 (DO NOT TAPER)
Patients ≥ 10 years ONLY:
- Prednisone (Sterapred) 30 mg/m2/dose PO twice per day on days 1 to 28 (DO NOT TAPER)
- Folinic acid (Leucovorin) 5 mg/m2 x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 10 - 11 and 31 - 32. (CNS3 also on days 17 - 18 and 24 - 25).
RER - M1 Marrow at Day 15
- Add Daunorubicin (Cerubidine) 50 mg/m2 IV over 1 to 15 minutes once on days 15.
CNS prophylaxis
- Cytarabine (Ara-C) as follows:
- 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) as follows:
- 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
Subsequent treatment
- See protocol for details of treatment beyond induction
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. link to original article link to PMC article PubMed NCT02883049
Consolidation
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on days 1 and 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, 36 - 39.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 - 2 hours once on days 15, and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.
- Mercaptopurine (6-MP) 60 mg/m2/dose PO once per day on days 1 - 14, and 29 - 42.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15, and 22.
Age | 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/m2 x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 3 - 4, 10 - 11, 17 - 18, and 24 - 25.
56-Day Course
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. link to original article link to PMC article PubMed NCT02883049
- 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. link to original article contains verified protocol PubMed NCT01190930
Interim Maintenance with ID MTX
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.
- Mercaptopurine (6-MP) 25 mg/m2/dose PO once per day on days 1 - 56.
- Intermediate Dose Methotrexate (MTX) 2,000 mg/m2 IV over 24 hours on days 1, 15, 29, and 43.
- Methotrexate 200 mg/m2 IV infused over 30 minutes. This is followed, immediately, by methotrexate 1,800 mg/m2 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/m2 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, and 45 - 46.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 and 29.
Age | 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
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. link to original article link to PMC article PubMed NCT02883049
- 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. link to original article contains verified protocol PubMed NCT01190930
Delayed Intensification
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV push over 1 to 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours once on days 4 and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 - 7 and 15 - 21.
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 - 60 minutes once on day 29 ONLY.
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.
- Thioguanine (Tabloid) 60 mg/m2/day PO once per day on days 29 to 42.
- Folinic acid (Leucovorin) 5 mg/m2 x 2 doses PO or IV (given at 48, and 60 hours after the lumbar puncture) on days 3 - 4, 31 - 32, and 38 - 39.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 29, and 36.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
56-Day course
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. link to original article link to PMC article PubMed NCT02883049
DS HR Arm Maintenance
Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | Randomized portion of RCT |
Radiotherapy
For Patients with CNS3 Disease
- Total body irradiation (TBI) 1,800 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/m2/dose PO once per day on days 1 - 84.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on day 1 ONLY.
- Methotrexate (MTX) 20 mg/m2 PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).
- Prednisone (Sterapred) 20 mg/m2/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5.
CNS 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).
Age | 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.
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. link to original article link to PMC article PubMed NCT02883049
Prephase
Methylprednisolone monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Place et al. 2015 (DFCI 05-001) | 2005-2011 | Non-randomized portion of RCT |
Burns et al. 2020 (DFCI 11-001) | 2012-2015 | 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.
Chemotherapy
- Methylprednisolone (Solumedrol) 8 mg/m2 IV three times per day on days 1 to 3
3-day course
Subsequent treatment
- DFCI 05-001: Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Methylprednisolone induction versus Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone induction
- DFCI 11-001: Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone induction versus Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone induction
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. link to original article 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. link to original article contains verified protocol in supplement 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. link to original article contains verified protocol in supplement PubMed NCT01574274
Prednisone monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Möricke et al. 2016 (AIEOP-BFM ALL 2000) | 2000-2006 | Non-randomized portion of RCT |
Chemotherapy
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 7
CNS prophylaxis
- Methotrexate (MTX) 15 mg IT once on day 1
7-day course
Subsequent treatment
- Daunorubicin, L-Asparaginase, Vincristine, Prednisone versus Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone induction
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. link to original article contains verified protocol in supplement PubMed NCT00430118; NCT00613457
Vincristine & Prednisone
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VP: Vincristine & Prednisone
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Sallan et al. 1978 | 1973-1977 | 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.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Prednisone (Sterapred) 40 mg/m2/day PO on days 1 to 21
21-day course
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. link to original article contains verified protocol PubMed
Upfront induction therapy
Calaspargase, Daunorubicin, Vincristine, Prednisone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Angiolillo et al. 2014 (COG AALL07P4) | 2008-2010 | Randomized (E-RT-switch-ic) | Daunorubicin, Pegaspargase, Vincristine, Prednisone | Longer half-life |
Chemotherapy
- Calaspargase (Asparlas) 2500 units/m2 IV once on day 4
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
- Prednisone (Sterapred) 30 mg/m2 PO twice per day on days 1 to 28
5-week course
Subsequent treatment
- See protocol for details of treatment beyond induction
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. link to original article link to PMC article contains verified protocol PubMed NCT00671034
Daunorubicin, Pegaspargase, Vincristine, Dexamethasone
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Regimen
Study | Evidence |
---|---|
Burke et al. 2019 (COG AALL1131) | 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.
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
- Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours once on day 4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
- Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 14
CNS prophylaxis
- Cytarabine (Ara-C) as follows:
- 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) as follows:
- 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
Subsequent treatment
- See protocol for details of treatment beyond induction
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. link to original article link to PMC article PubMed NCT02883049
DOLP
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DOLP: Daunorubicin, Oncovin (Vincristine), L-Asparaginase, Prednisone
DVPA: Daunorubicin, Vincristine, Prednisone, Asparaginase
Regimen variant #1, 25/1.5/6000/60
Study | Evidence |
---|---|
Seibel et al. 2008 (COG CCG-1961) | Non-randomized portion of RCT |
Note: exact days were not specified for the L-asparaginase; suggested days are similar to those used in subsequent parts of the protocol.
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
- Asparaginase (Elspar) 6000 units/m2 IM once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 28
CNS therapy
- Cytarabine (Ara-C) IT once on day 0 (dose not specified)
- Methotrexate (MTX) IT once per day on days 7 & 28 (dose not specified)
4-week course
Subsequent treatment
- Standard versus increased intensity post-remission therapy (see paper for details)
Regimen variant #2, 30/1.5/5000/60 ("Phase A" of ALL-BFM 95; "Phase 1" of ALL IC-BFM 2002)
Study | Years of enrollment | Evidence |
---|---|---|
Möricke et al. 2008 (ALL-BFM 95) | 1995-2000 | Non-randomized |
Stary et al. 2013 (ALL IC-BFM 2002) | 2002-2007 | 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.
Chemotherapy
- Daunorubicin (Cerubidine) 30 mg/m2 IV over 60 minutes once per day on days 8, 15, 22, 29
- Vincristine (Oncovin) 1.5 mg/m2 (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
- Prednisone (Sterapred) 60 mg/m2/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
Subsequent treatment
- See papers for details
Regimen variant #3, 30/1.5/10,000/60 ("Protocol I")
Study | Evidence |
---|---|
Schrappe et al. 2000 (ALL-BFM 90) | Non-randomized |
Kamps et al. 2002 (DCLSG ALL-8) | Non-randomized |
Note: see papers for details on dose adjustments based on risk.
Chemotherapy
- Daunorubicin (Cerubidine) 30 mg/m2 IV over 60 minutes once per day on days 8, 15, 22, 29
- Vincristine (Oncovin) 1.5 mg/m2 (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
- Prednisone (Sterapred) 60 mg/m2/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
Subsequent treatment
- See papers for details
Regimen variant #4, 40/1.5/10,000/60 ("Induction Protocol I" of ALL-BFM 86)
Study | Evidence |
---|---|
Reiter et al. 1994 (ALL-BFM 86) | Non-randomized portion of RCT |
Kamps et al. 1999 (DCLSG ALL-7) | Non-randomized portion of RCT |
Chemotherapy
- Daunorubicin (Cerubidine) 40 mg/m2 IV once per day on days 8, 15, 22, 29
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29
- L-Asparaginase 10,000 units/m2 IV once per day on days 19, 22, 25, 28, 31, 34, 37, 40
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 28
6-week course
Subsequent treatment
- Induction phase II (see papers for details)
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. link to original article contains verified protocol 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. link to original article 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. link to original article contains verified protocol 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. link to original article 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. link to original article refers to ALL-BFM 90 protocol 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. link to original article link to PMC article contains verified protocol 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. link to original article contains verified protocol 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. link to original article PubMed
- 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. link to original article contains verified protocol PubMed NCT00764907
DOLP (Prednisolone)
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DOLP: Daunorubicin, Oncovin (Vincristine), L-Asparaginase, Prednisolone
Regimen variant #1, 30/10,000/1.5/60
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Moerloose et al. 2010 (EORTC CLG 58951) | 1999-2002 | Phase III (C) | Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone | 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.
Chemotherapy
- Daunorubicin (Cerubidine) 30 mg/m2 IV once per day on days 8, 15, 22, 29
- Vincristine (Oncovin) 1.5 mg/m2 (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
- Prednisolone (Millipred) 60 mg/m2/day PO on days 1 to 28, then tapered over 9 days
5-week course
Subsequent treatment
- See paper for details
Regimen variant #2, 45/6000/1.5/40
Study | Evidence |
---|---|
Chessells et al. 1992 (UK MRC ALLX) | Non-randomized portion of RCT |
Note: exact days for L-asparaginase were not specified in the protocol.
Chemotherapy
- Daunorubicin (Cerubidine) 45 mg/m2 IV once per day on days 1 & 2
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Asparaginase (Elspar) 6000 units/m2 SC once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21
- Prednisolone (Millipred) 40 mg/m2/day PO on days 1 to 28
29-day course
Subsequent treatment
- Intensification (randomized) or Cy/TBI with allo HSCT, depending on donor availability
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. link to original article contains verified protocol 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. link to original article 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. link to original article link to PMC article contains verified protocol 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/m2/day) and prednisolone (60 mg/m2/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. link to original article link to PMC article 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. link to original article link to PMC article PubMed
Doxorubicin, Mercaptopurine, Pegaspargase, Vincristine, Prednisolone
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Albertsen et al. 2019 (NOPHO ALL2008) | 2008-2016 | Non-randomized portion of RCT |
See protocol for initiation dependencies of 6-MP and pegaspargase.
Chemotherapy
- Doxorubicin (Adriamycin) 40 mg/m2 IV over 4 hours once per day on days 1 & 22
- Mercaptopurine (6-MP) 25 mg/m2 PO once per day on days 30 to 35
- Pegaspargase (Oncaspar) 1000 units/m2 IM once on day 30
- Vincristine (Oncovin) as follows:
- Younger than 18: 2 mg/m2 (maximum dose of 2.5 mg) IV once per day on days 1, 8, 15, 22, 29
- 18 or older: 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29
- Prednisolone (Millipred) 20 mg/m2 PO three times per day on days 1 to 29, then 10 mg/m2 PO three times per day on days 30 to 32, then 5 mg/m2 PO three times per day on days 33 to 35, then 2.5 mg/m2 PO three times per day on days 36 to 38
CNS prophylaxis
- Methotrexate (MTX) as follows:
- 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
Subsequent treatment
- See protocol for details of treatment beyond induction
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. link to original article contains verified protocol in supplement PubMed NCT00819351
Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Place et al. 2015 (DFCI 05-001) | 2005-2011 | Phase III (E-switch-ic) | Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Methylprednisolone | Did not meet secondary endpoint of DFS | Less anxiety |
Burns et al. 2020 (DFCI 11-001) | 2012-2015 | Phase III (C) | Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone | 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.
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 4 & 5
- Methotrexate (MTX) 40 mg/m2 IV once on day 6
- Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 7
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 4, 11, 18, 25
- Methylprednisolone (Solumedrol) 8 mg/m2 IV three times per day on days 4 to 32
Supportive medications
- Dexrazoxane (Zinecard) 300 mg/m2 IV once per day on days 4 & 5
28-day course
CNS 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
Subsequent treatment
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. link to original article 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. link to original article contains verified protocol in supplement 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. link to original article contains verified protocol in supplement PubMed NCT01574274
Pegaspargase, Vincristine, Dexamethasone
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Maloney et al. 2019 (COG AALL0331) | 2005-2010 | Non-randomized portion of RCT |
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Note: there are very minor differences in timing between protocols; see papers for details.
Chemotherapy
- Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
- Dexamethasone (Decadron) 3 mg/m2 PO twice per day on days 1 to 28
CNS 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
Subsequent treatment
- COG AALL0331, M2 marrow or M1 marrow with MRD of at least 1% at day 29: Extended induction
- COG AALL0932: 6-MP & Vincristine consolidation
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. link to original article link to PMC article contains verified protocol 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. link to original article contains verified protocol PubMed NCT01190930
Pegaspargase, Vincristine, Prednisone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Avramis et al. 2002 (CCG 1962) | 1997-1998 | Randomized (E-RT-switch-ic) | L-Asparaginase, Vincristine, Prednisone | 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.
Chemotherapy
Subsequent treatment
- See protocol for details of treatment beyond induction
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. link to original article PubMed
Early intensification therapy
Cyclophosphamide, Etoposide, Methotrexate
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dreyer et al. 2014 (COG P9407) | 2001-2006 | Non-randomized | ||
Brown et al. 2021 (COG AALL0631) | 2008-2014 | Phase III (C) | Cyclophosphamide, Etoposide, Lestaurtinib, Methotrexate | Did not meet primary endpoint of EFS |
Biomarker eligibility criteria
- COG AALL0631: KMT2A rearrangement
Preceding treatment
- Induction
Chemotherapy
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV over 30 minutes once per day on days 15 to 19
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 15 to 19
- Methotrexate (MTX) 200 mg/m2 IV over 20 minutes, then 3800 mg/m2 IV continuous infusion over 23 hours and 40 minutes on days 1 & 8 (total dose: 8000 mg/m2)
Subsequent treatment
- Reinduction
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. link to original article link to PMC article 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. link to original article contains verified protocol in supplement PubMed NCT00557193
Mercaptopurine & Methotrexate
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mahoney et al. 1998 (POG 9005) | 1991-1993 | Phase III (E-switch-ic) | LDMTX/IVMP | Seems to have superior CCR |
Lauer et al. 2001 (POG 9006) | 1991-1994 | Phase III (C) | Intensive chemotherapy | Might have inferior EFS |
Preceding treatment
- POG 9006: DOLP induction
Chemotherapy
Subsequent treatment
- POG 9006: 6-MP & MTX maintenance
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. link to original article 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. link to original article 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
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Regimen
Study | Evidence |
---|---|
Larsen et al. 2016 (COG AALL0232) | Non-randomized portion of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 1 & 29
- Cytarabine (Ara-C) 75 mg/m2 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/m2 PO once per day on days 1 to 14, 29 to 42
- Pegaspargase (Oncaspar) 2500 units/m2 IM or IV once per day on days 15 & 43
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50
50-day course
Subsequent treatment
- 6-MP, Capizzi MTX, Pegaspargase, Vincristine interim maintenance versus 6-MP, HD-MTX, Vincristine interim maintenance
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. link to original article link to PMC article contains verified protocol PubMed NCT00075725
Augmented BFM consolidation
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nachman et al. 1998 | 1991-1995 | Phase III (E-esc) | Standard BFM consolidation | Seems to have superior OS |
Unlikely to be completed, but of historic interest.
Chemotherapy
- Cyclophosphamide (Cytoxan)
- Cytarabine (Ara-C)
- Asparaginase (Elspar)
- Mercaptopurine (6-MP)
- Vincristine (Oncovin)
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. link to original article PubMed
Cyclophosphamide & TBI, then allo HSCT
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Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Thomas et al. 1979 | 1976-1977 | Non-randomized |
Details in most of the manuscripts are limited.
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation by the following study-specific criteria:
- Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
- Other studies: 10 to 1200 cGy total
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Immunotherapy
Stem cells transfused on day 0
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. link to original article contains protocol PubMed
Etoposide & TBI, then allo HSCT
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Balduzzi et al. 2005 | 1995-2000 | Quasi-randomized | Chemotherapy | Seems to have superior DFS |
Peters et al. 2015 (ALL-SCT-BFM 2003) | 2003-2011 | Non-randomized |
Chemotherapy
- Etoposide (Vepesid) 60 mg/kg (maximum dose of 3600 mg) IV once on day -3
Radiotherapy
- Total body irradiation (TBI) 200 cGy twice per day in 6 fractions on days -6 to -4 with lung shielding at 1000 cGy (total dose: 1200 cGy)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Immunotherapy
Stem cells transfused on day 0
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. link to original article contains verified protocol 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. link to original article PubMed NCT01423747
Mercaptopurine & Vincristine
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Mercaptopurine (6-MP) 75 mg/m2/day PO on days 1 to 28
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once on day 1
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15
28-day course
Subsequent treatment
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. link to original article contains verified protocol PubMed NCT01190930
Interim maintenance
Mercaptopurine, Methotrexate, Vincristine
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Larsen et al. 2016 (COG AALL0232) | 2004-2011 | Phase III (E-switch-ic) | Mercaptopurine, Capizzi MTX, Pegaspargase, Vincristine | Superior EFS |
Chemotherapy
- Mercaptopurine (6-MP) 25 mg/m2 PO once per day on days 1 to 56
- Methotrexate (MTX) 5000 mg/m2 IV once per day on days 1, 15, 29, 43
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43
Intrathecal component
- Methotrexate (MTX) once per day on days 1 & 29
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. link to original article link to PMC article contains verified protocol PubMed NCT00075725
Methotrexate & Vincristine
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Matloub et al. 2011 (COG CCG-1991) | 2000-2005 | Phase III (E-de-esc) | Mercaptopurine, MTX, Vincristine, Dexamethasone | Superior EFS |
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
- COG AALL0932: 6-MP & Vincristine consolidation
Chemotherapy
- Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
CNS prophylaxis
- Methotrexate (MTX) IT once on day 31
8-week course
Subsequent treatment
- COG AALL0932: AALL0932 delayed intensification
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. link to original article link to PMC article 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. link to original article contains verified protocol PubMed NCT01190930
Delayed intensification
AALL0932 delayed intensification
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV on days 29 to 32, 36 to 39
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1, 8, 15
- Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 4
- Thioguanine (Tabloid) 60 mg/m2/day PO on days 29 to 42
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Dexamethasone (Decadron) 10 mg/m2/day PO on days 1 to 7, 15 to 21
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 & 29
8-week course
Subsequent treatment
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. link to original article contains verified protocol PubMed NCT01190930
Interim maintenance II
Methotrexate & Vincristine
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Angiolillo et al. 2021 (COG AALL0932) | 2010-2018 | 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.
Preceding treatment
Chemotherapy
- Methotrexate (MTX) 200 mg/m2 IV once on day 1, then 250 mg/m2 IV once on day 11, then 300 mg/m2 IV once on day 21, then 350 mg/m2 IV once on day 31, then 400 mg/m2 IV once on day 41
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1 & 31
8-week course
Subsequent treatment
- Randomization to one of four maintenance arms; see paper for details.
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. link to original article contains verified protocol PubMed NCT01190930
Maintenance after upfront therapy
Mercaptopurine & Methotrexate
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Millot et al. 2001 (EORTC 58881) | 1990-1996 | Phase III (C) | 6-MP & MTX; IV 6-MP & PO MTX | Superior DFS1 |
Conter et al. 2007 (I-BFM-SG IR ALL) | 1995-2000 | Phase III (C) | D-OMP | Did not meet primary endpoint of DFS |
1Reported efficacy for EORTC 58881 is based on the 2005 update.
Preceding treatment
- I-BFM-SG IR ALL: BFM re-induction
Chemotherapy
- Mercaptopurine (6-MP) 50 mg/m2 PO once per day
- Methotrexate (MTX) 20 mg/m2 PO once on day 1
7-day cycle for 74 cycles or a total of 2 years from start of treatment
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. link to original article 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. link to original article 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. link to original article 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. link to original article contains verified protocol PubMed NCT00411541
Observation
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2021 (CCCG-ALL-2015) | 2015-2020 | Phase III (E-de-esc) | Vincristine & Dexamethasone | 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.
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. link to original article PubMed ChiCTR-IPR-14005706
Relapsed or refractory
Blinatumomab monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
von Stackelberg et al. 2016 (MT103-205) | 2012-2014 | Phase I/II (RT) |
Note: this is the MTD of a phase I/II trial enrolling children under the age of 18.
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
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. link to original article contains verified protocol PubMed NCT01471782
CCE
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CCE: Clofarabine, Cyclophosphamide, Etoposide
Regimen
Study | Evidence |
---|---|
Locatelli et al. 2009 | Non-randomized |
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.
Chemotherapy
- Clofarabine (Clolar) 40 mg/m2 IV over 2 hours once per day on days 1 to 5, given first
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Etoposide (Vepesid) 150 mg/m2 IV over 2 hours once per day on days 1 to 5
Supportive medications
- Prophylactic steroids used for patients with greater than 30 x 109 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."
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. link to original article contains verified protocol PubMed
Clofarabine monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Jeha et al. 2003 | 2000-2002 | Phase 1, <20 pts (RT) |
Jeha et al. 2006 | 2002-2004 | Phase II (RT) |
Note: this dose was the MTD in Jeha et al. 2003.
Chemotherapy
- Clofarabine (Clolar) 52 mg/m2 IV over 2 hours once per day on days 1 to 5
2- to 6-week cycles, depending on response count recovery
References
- Phase 1: 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. link to original article PubMed
- 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. link to original article contains protocol PubMed
DOLP
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DOLP: Daunorubicin, Oncovin (Vincristine), L-Asparaginase, Prednisone
Regimen
Study | Evidence |
---|---|
Rivera et al. 1986 | Non-randomized |
Chemotherapy
4-week course
Subsequent treatment
- See paper for details of treatment beyond induction
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. link to original article PubMed
Doxorubicin, Pegaspargase, Vincristine, Prednisone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Abshire et al. 2000 (POG 9310) | NR | Non-randomized | ||
Raetz et al. 2008 (COG AALL01P2) | 2003-2005 | Non-randomized portion of RCT | ||
Lew et al. 2021 (COG AALL0433) | 2007-2013 | Phase III (C) | Doxorubicin, Pegaspargase, Vincristine, Prednisone; high-dose vincristine | 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.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 2, 9, 16, 23
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
- Prednisone (Sterapred) 40 mg/m2/day PO on days 1 to 29
CNS prophylaxis (CNS-)
- Methotrexate (MTX) once per day on days 8 & 29
CNS treatment (CNS+)
5-week course
Subsequent treatment
- See papers for details of treatment beyond induction block 1
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. link to original article 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. link to original article link to PMC article contains verified protocol 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. link to original article link to PMC article does not contain protocol PubMed NCT00381680
Inotuzumab ozogamicin monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Kantarjian et al. 2012 (MDACC 2009-0872) | 2010-2011 | Phase II |
Antibody-drug conjugate therapy
- Inotuzumab ozogamicin (Besponsa) 0.8 mg/m2 IV once on day 1, then 0.5 mg/m2 IV once per day on days 8 & 15
- For patients achieving CR or CRi, day 1 dose was reduced to 0.5 mg/m2
21-day cycle for 1 cycle, then 28-day cycle for up to 5 cycles
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. link to original article contains protocol PubMed NCT01134575
Mitoxantrone, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Parker et al. 2010 (CCLG ALL R3) | 2003-2007 | Phase III (E-switch-ic) | Idarubicin, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone | Superior OS |
Note: per the protocol, this regimen is intended only for patients 18 and younger. This regimen is for patients allergic to pegaspargase.
Chemotherapy
- Mitoxantrone (Novantrone) 10 mg/m2 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/m2 IV once per day on days 3, 10, 17, 24
- Dexamethasone (Decadron) 20 mg/m2 PO once per day on days 1 to 5, 15 to 19
CNS prophylaxis
- Methotrexate (MTX) as follows:
- 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
Subsequent treatment
- See paper for details of treatment beyond induction
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. link to original article contains verified protocol link to PMC article PubMed NCT00967057
Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Parker et al. 2010 (CCLG ALL R3) | 2003-2007 | Phase III (E-switch-ic) | Idarubicin, Pegaspargase, Vincristine, Dexamethasone | Superior OS |
Note: per the protocol, this regimen is intended only for patients 18 and younger.
Chemotherapy
- Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 & 8
- Pegaspargase (Oncaspar) 1000 units/m2 IM once per day on days 3 & 18
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 3, 10, 17, 24
- Dexamethasone (Decadron) 20 mg/m2 PO once per day on days 1 to 5, 15 to 19
CNS prophylaxis
- Methotrexate (MTX) as follows:
- 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
Subsequent treatment
- See paper for details of treatment beyond induction
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. link to original article contains verified protocol link to PMC article PubMed NCT00967057
Tisagenlecleucel monotherapy
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Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Grupp et al. 2013 (Pedi CART19) | 2011-NR | Pilot | |
Maude et al. 2014 (UPCC04409) | 2012-2014 | Phase I/IIa | |
Maude et al. 2018 (ELIANA) | 2015-2017 | Phase II (RT) | ORR: 81% |
Note: dosing instructions are based on ELIANA.
Preceding treatment
Immunotherapy
- Tisagenlecleucel (Kymriah) as follows:
- Up to 50 kg: 2 to 5 x 106 CTL019 transduced viable T-cells per kg body weight IV once on day 0
- Greater than 50 kg: 1.0 to 2.5 x 108 CTL019 transduced viable T-cells IV once on day 0
One course
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. link to original article link to PMC article 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. link to original article link to PMC article 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. link to original article link to supplementary protocol contains verified protocol in supplement link to PMC article PubMed NCT02435849
Consolidation after salvage therapy
Blinatumomab monotherapy
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Regimen variant #1, 1 cycle
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Locatelli et al. 2021 (Amgen 20120215) | 2015-2019 | Phase III (E-switch-ooc) | Standard salvage consolidation chemotherapy | Superior EFS |
Immunotherapy
- Blinatumomab (Blincyto) 15 mcg/m2/day IV continuous infusion over 28 days, started on day 1 (total dose: 420 mcg/m2)
42-day course
Subsequent treatment
- Allogeneic hematopoietic stem cell transplant
Regimen variant #2, 2 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Brown et al. 2021 (COG AALL1331) | 2014-2019 | Phase III (E-switch-ooc) | Standard salvage consolidation chemotherapy | Might have superior DFS |
Note: insufficient dosing information was present in the abstract.
Immunotherapy
Subsequent treatment
- Allogeneic hematopoietic stem cell transplant
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. link to original article 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. link to original article contains protocol PubMed NCT02393859
Cyclophosphamide & TBI, then allo HSCT
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Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 1981 | 1976-1980 | Non-randomized | ||
Kersey et al. 1987 | 1982-1985 | Quasi-randomized | Auto HSCT | Superior RFS |
Details in most of the manuscripts are limited.
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation by the following study-specific criteria:
- Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
- Other studies: 10 to 1200 cGy total
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Immunotherapy
Stem cells transfused on day 0
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. link to original article PubMed
- 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. link to original article PubMed
Further notes
Pediatric ALL regimens tend to be very complex. This list on ped-onc.org appears to be fairly comprehensive and includes regimen details for some of the common regimens e.g. COG-AALL0232. For now we will try to include a list of references here and potentially build these regimens here, over time.