T-cell acute lymphoblastic leukemia, pediatric
Section editor transclusions This page contains studies that were specific to pediatric populations. For the more general T-cell acute lymphoblastic leukemia page, follow this link.
16 regimens on this page
17 variants on this page
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Guidelines
"How I Treat"
- 2020: Teachey & O'Connor How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children
- 2020: Hunger & Raetz. How I treat relapsed acute lymphoblastic leukemia in the pediatric population
NCCN
COG AALL0434
Arms B (Nelarabine Arms)
Induction
All Patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Non-randomized portion of RCT |
Chemotherapy
- Pegaspargase (Oncaspar) 2,500 units/m2 IV once on day 4 (OR 5 OR 6)
- 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/dose PO twice per day on days 1 to 28 (Total of 60 mg/m2/day, DO NOT TAPER)
- Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
CNS prophylaxis
- Cytarabine (Ara-C) IT once given at time of diagnostic lumbar puncture or Day 1
Age | Initial Dose |
---|---|
1 - 1.99 years | 30 mg |
2 - 2.99 years | 50 mg |
≥ 3 years | 70 mg |
- Methotrexate (MTX) IT once per day on days 8 & 29 (CNS3 patients on days 15 and 22 ALSO)
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
29 Day Course
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Consolidation
Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (E-esc) | Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV once per day over 30 minutes on days 8 & 50
- Must reduce urine specific gravity to ≤ 1.015 prior to administration
- Cytarabine (Ara-C) 75 mg/m2 IV over 1 - 30 minutes or SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
- Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
- DO NOT escalate or modify dose based on blood counts during this course.
- Nelarabine (Arranon) 650 mg/m2 IV once per day over 60 minutes on days 1 to 5, 43 to 47
- Pegaspargase (Oncaspar) 2,500 units/m2 IM or IV over 1 - 2 hours once per day on days 22 & 64
- Vincristine (Oncovin) 1.5 mg/m2 (MAX 2 mg) IV once per day on days 22, 29, 64, 71
CNS prophylaxis
- Methotrexate (MTX) IT on days 15, 22, 57, 64 (Omit Day 22 if CNS3 T-ALL)
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
- Whole-brain irradiation
- CNS3 T-ALL: 1,800cGy in 10 once daily fractions.
- Intermediate/High Risk ARM B: 1,200 cGy in 8 once-daily fractions given during weeks 4 and 5 of consolidation
71-day course
Subsequent treatment
- Interim maintenance; see paper for details
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Interim Maintenance with Capizzi MTX
Arms A and B
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (E-esc) | Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
Preceding treatment
- Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine induction
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
- If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41
- Pegaspargase (Oncaspar) 2,500 units/m2 IM or IV over 1 - 2 hours once per day on days 2 and 22.
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Delayed Intensification (Nelarabine Arms)
Arm B and D
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (E-esc) | Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) 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 (10 mg/m2/day, divided BID).
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 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 IM or IV over 1 - 2 hours on day 4 (OR 5 OR 6) AND day 43.
- Thioguanine (Tabloid) 60 mg/m2/day PO once per day on days 29 to 42
- Should not be given to patients receiving CRT (Arm D and CNS3 T-ALL patients).
- Nelarabine (Arranon) 650 mg/m2 IV 60 minutes once per day on days 29 - 33.
CNS prophylaxis
- Methotrexate (MTX) IT once 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 |
Radiotherapy
- Arm D Only: Total body irradiation (TBI) 1,200 cGy in 8 once daily fractions to start on day 50 of DI.
- CNS3 T-ALL: Total body irradiation (TBI) 1,800 cGy in 10 once daily fractions to start on day 50 of DI.
63 Day Course
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Maintenance Arms
Arms B and D
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (E-esc) | Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1 and 57.
- Prednisone (Sterapred) 20 mg/m2/dose PO twice per day on days 1 - 5 and 57 - 61 (Total of 40 mg/m2/day, divided BID)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 to 28 and 36 - 84.
- Methotrexate (MTX) 20 mg/m2/dose PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, and 78.
- No dose escalation recommended for the first maintenance cycle.
- Thereafter, for ANC ≥ 1,500μL on 3 CBCs done over 6 weeks or 2 monthly CBCs, increase dose of methotrexate or mercaptopurine by 25%.
- Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 29 - 33.
- DO NOT Administer with other Chemotherapy agents.
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 |
Repeat above cycle for a total of 3 cycles.
3 Cycles
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Continued Maintenance
Arms B and D after Cycle 3
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (E-esc) | Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1, 29, and 57.
- Prednisone (Sterapred) 20 mg/m2/dose PO twice per day on days 1 - 5, 29 - 33, and 57 - 61. (Total of 40 mg/m2/day, divided BID)
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 84.
- Methotrexate (MTX) 20 mg/m2/dose PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
- No dose escalation recommended for the first maintenance cycle.
- Thereafter, for ANC ≥ 1,500μL on 3 CBCs done over 6 weeks or 2 monthly CBCs, increase dose of methotrexate or mercaptopurine by 25%.
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 |
Duration
- Girls T-ALL: Continue repeating 12 week cycles of maintenance therapy II until the total duration of therapy is two years from the start of Interim Maintenance (~ Week 121)
- Boys T-ALL: Continue to repeat 12 week cycles of Maintenance therapy II until the total duration of therapy is three years from the start of Interim Maintenance (~ Week 173).
- T-NHL patients (regardless of gender): Continue to repeat 12 week cycles of maintenance therapy II until the total duration reaches two years from the start of Interim Maintenance (~ Week 121)
84 Day Course
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
COG AALL1231 Arm A
Induction
All T-ALL and T-LLy patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 - 2 hours once on day 4 and 18.
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, and 22.
- Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 28 (DO NOT TAPER).
- Daunorubicin (Cerubidine) 25 mg/m2 IV over 1 to 15 minutes once per day on days 1, 8, 15, and 22.
CNS prophylaxis
- Cytarabine (Ara-C) IT once on day 1 or at the time of diagnostic lumbar puncture (if within 72 hours of protocol initiation).
Age | Initial Dose |
---|---|
1 - 1.99 years | 30 mg |
2 - 2.99 years | 50 mg |
≥ 3 years | 70 mg |
- Methotrexate (MTX) IT once per day on days 8 & 29
- CNS3 patients also receive Methotrexate (MTX) IT on days 15 and 22.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Consolidation
All T-ALL and T-LLy Patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1,000 mg/m2/dose IV once per day over 30 - 60 minutes on days 1 and 29.
- Cytarabine (Ara-C) 75 mg/m2/dose IV over 1 - 30 minutes or SC once per day 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.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours once per day on days 15 and 43.
- Vincristine (Oncovin) 1.5 mg/m2 (MAX 2 mg) IV once per day on days on days 15, 22, 43, and 50.
CNS prophylaxis
- Methotrexate (MTX) IT once per day on days 1, 8, 15 & 22
- CNS3 patients and CNS3 T-LLy: Omit days 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
SR Patients
Interim Maintenance with CMTX
SR Patients Receive After Consolidation
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
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.
- If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose.
- Vincristine (Oncovin) 1.5 mg/m2/dose (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, and 41.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours once per day on days 2 and 22.
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Delayed Intensification
All T-ALL and T-LLy Patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2/dose IV or PO twice per day on days 1 - 7 and 15 - 21 (10 mg/m2/day, divided BID).
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 minutes once on day 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 to 32 and 36 to 39
- Doxorubicin (Adriamycin) 25 mg/m2/dose IV push/infusion over 1 - 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours on day 4, 18, AND day 43.
- Thioguanine (Tabloid) 60 mg/m2/dose PO once per day on days 29 to 42
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
IR Patients
Delayed Intensification
All T-ALL and T-LLy Patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2/dose IV or PO twice per day on days 1 - 7 and 15 - 21 (10 mg/m2/day, divided BID).
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 minutes once on day 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 to 32 and 36 to 39
- Doxorubicin (Adriamycin) 25 mg/m2/dose IV push/infusion over 1 - 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours on day 4, 18, AND day 43.
- Thioguanine (Tabloid) 60 mg/m2/dose PO once per day on days 29 to 42
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Interim Maintenance #1 with HDMTX - ALL IR Patients
SR and VHR T-ALL and T-LLy DO NOT RECEIVE
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
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.
- 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 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Interim Maintenance #2 with CMTX - ALL IR Patients
IR T-ALL and T-LLy Patients receive this after DI as IM#2
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
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.
- If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose.
- Vincristine (Oncovin) 1.5 mg/m2/dose (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, and 41.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours once per day on days 2 and 22.
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
VHR Patients
Intensification Block 1
VHR Patients receive immediately after consolidation
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Dexamethasone (Decadron) 10 mg/m2/dose IV or PO twice per day on days 1 - 5 (20 mg/m2/day, divided BID).
- High Dose Methotrexate (MTX) 5,000 mg/m2 IV over 24 hours on day 1 ONLY.
- 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.
- 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.
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1 and 6.
- Cyclophosphamide (Cytoxan) 200 mg/m2/dose every 12 hours IV over 1 - 6 hours x 5 doses on days 2 - 4.
- High Dose Cytarabine (Ara-C) 2,000 mg/m2/dose every 12 hours IV over 3 hours x 2 doses on day 5.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours on day 6.
- Administer 3 hours after completion of the second high dose Cytarabine infusion
- Filgrastim (Neupogen) 5 mcg/kg/dose SC or IV daily beginning on day 7 and until WBC > 3000μL
- Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Max 6 mg/dose) SC once during the 7 - 11th day.
Triple Intrathecal Therapy
Given on day 1, 2 hours after the start of HD MTX infusion
- 1 to < 2 yrs
- Methotrexate (MTX): 8 mg
- Hydrocortisone (Cortef): 8 mg
- Cytarabine (Ara-C): 16 mg
- 2 to < 3 yrs:
- Methotrexate (MTX): 10 mg
- Hydrocortisone (Cortef): 10 mg
- Cytarabine (Ara-C): 20 mg
- 3 to < 9 yrs:
- Methotrexate (MTX): 12 mg
- Hydrocortisone (Cortef): 12 mg
- Cytarabine (Ara-C): 24 mg
- ≥ 9 yrs:
- Methotrexate (MTX): 15 mg
- Hydrocortisone (Cortef): 15 mg
- Cytarabine (Ara-C): 30 mg
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Intensification Block 2
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Dexamethasone (Decadron) 10 mg/m2/dose IV or PO twice per day on days 1 - 5 (20 mg/m2/day, divided BID).
- High Dose Methotrexate (MTX) 5,000 mg/m2 IV over 24 hours on day 1 ONLY.
- 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.
- 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.
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1 and 6.
- Ifosfamide (Ifex) 800 mg/m2/dose every 12 hours IV infusion over 1 hour x 5 doses on days 2 - 4.
- Start Immediately after completion of high dose methotrexate infusion.
- Mesna (Mesnex) 300 mg/m2/dose at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 2 - 4.
- Daunorubicin (Cerubidine) 30 mg/m2/dose IV over 1 - 15 minutes on day 5.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours on day 6.
- Filgrastim (Neupogen) 5 mcg/kg/dose SC or IV daily beginning on day 7 and until WBC > 3000μL
- Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Max 6 mg/dose) SC once during the 7 - 11th day.
Triple Intrathecal Therapy
Given on day 1, 2 hours after the start of HD MTX infusion
- 1 to < 2 yrs
- Methotrexate (MTX): 8 mg
- Hydrocortisone (Cortef): 8 mg
- Cytarabine (Ara-C): 16 mg
- 2 to < 3 yrs:
- Methotrexate (MTX): 10 mg
- Hydrocortisone (Cortef): 10 mg
- Cytarabine (Ara-C): 20 mg
- 3 to < 9 yrs:
- Methotrexate (MTX): 12 mg
- Hydrocortisone (Cortef): 12 mg
- Cytarabine (Ara-C): 24 mg
- ≥ 9 yrs:
- Methotrexate (MTX): 15 mg
- Hydrocortisone (Cortef): 15 mg
- Cytarabine (Ara-C): 30 mg
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Intensification Block 3
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Dexamethasone (Decadron) 10 mg/m2/dose IV or PO twice per day on days 1 - 5 (20 mg/m2/day, divided BID).
- High Dose Cytarabine (Ara-C) 2,000 mg/m2/dose every 12 hours IV over 3 hours x 4 doses on days 1 - 2.
- Etoposide (Vepesid) 100 mg/m2/dose every 12 hours IV over 1 - 2 hours x 5 doses on days 3 - 5.
- First dose to be given 12 hours after the start of the 4th HD Cytarabine on day 2.
- Infusion rate should not exceed 300 mg/m2/hour (10 mg/kg/hour).
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours on day 6.
- Filgrastim (Neupogen) 5 mcg/kg/dose SC or IV daily beginning on day 7 and until WBC > 3000μL
- Alternative: Pegfilgrastim (Neulasta) 100 mcg/kg (Max 6 mg/dose) SC once during the 7 - 11th day.
Triple Intrathecal Therapy
Given on day 1, 2 hours after the start of HD MTX infusion
- 1 to < 2 yrs
- Methotrexate (MTX): 8 mg
- Hydrocortisone (Cortef): 8 mg
- Cytarabine (Ara-C): 16 mg
- 2 to < 3 yrs:
- Methotrexate (MTX): 10 mg
- Hydrocortisone (Cortef): 10 mg
- Cytarabine (Ara-C): 20 mg
- 3 to < 9 yrs:
- Methotrexate (MTX): 12 mg
- Hydrocortisone (Cortef): 12 mg
- Cytarabine (Ara-C): 24 mg
- ≥ 9 yrs:
- Methotrexate (MTX): 15 mg
- Hydrocortisone (Cortef): 15 mg
- Cytarabine (Ara-C): 30 mg
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Delayed Intensification
All T-ALL and T-LLy Patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1, 8, 15, 43, and 50.
- Dexamethasone (Decadron) 5 mg/m2/dose IV or PO twice per day on days 1 - 7 and 15 - 21 (10 mg/m2/day, divided BID).
- Cyclophosphamide (Cytoxan) 1,000 mg/m2 IV over 30 minutes once on day 29
- Cytarabine (Ara-C) 75 mg/m2/day SC or IV over 1 - 30 minutes on days 29 to 32 and 36 to 39
- Doxorubicin (Adriamycin) 25 mg/m2/dose IV push/infusion over 1 - 15 minutes once per day on days 1, 8, and 15.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours on day 4, 18, AND day 43.
- Thioguanine (Tabloid) 60 mg/m2/dose PO once per day on days 29 to 42
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Interim Maintenance with CMTX
VHR Patients receive after DI
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
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.
- If delay is necessary for myelosuppression and/or Grade 3 mucositis, discontinue escalation and resume at 80% of last dose.
- Vincristine (Oncovin) 1.5 mg/m2/dose (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, and 41.
- Pegaspargase (Oncaspar) 2,500 units/m2/dose IV over 1 - 2 hours once per day on days 2 and 22.
CNS prophylaxis
- Methotrexate (MTX) IT once 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 AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Maintenance - All Patients
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2/dose (max dose 2 mg) on days 1, 29, and 57.
- Dexamethasone (Decadron) 3 mg/m2/dose IV or PO twice per day on days 1 - 5, 29 - 33, and 57 - 61 (6 mg/m2/day, divided BID).
- Mercaptopurine (6-MP) 75 mg/m2/dose PO once per day on days 1 - 84.
- Methotrexate (MTX) 20 mg/m2/dose once weekly on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
- Omit day 29 of the first FOUR cycles for SR T-ALL and T-LLy patients.
- Omit day 29 of the first TWO cycles for IR T-ALL and T-LLy patients.
CNS prophylaxis
- Methotrexate (MTX) IT once on days 1.
- Also on day 29 of the first FOUR cycles for SR patients.
- Also on day 29 of the first TWO cycles for IR patients.
Age | Dose |
---|---|
1 - 1.99 | 8 mg |
2 - 2.99 | 10 mg |
3 - 8.99 | 12 mg |
≥ 9 | 15 mg |
Radiotherapy
ONLY the following groups receive CRT during the first cycle of maintenance.
- T-ALL Patients
- CNS1 VHR: Total body irradiation (TBI) 1,200 cGy
- CNS2 VHR: Total body irradiation (TBI) 1,200 cGy
- CNS3 IR: Total body irradiation (TBI) 1,800 cGy
- CNS3 VHR: Total body irradiation (TBI) 1,800 cGy
- T-LLy Patients
- CNS3 IR: Total body irradiation (TBI) 1,800 cGy
- CNS3 VHR: Total body irradiation (TBI) 1,800 cGy
Duration of therapy
- SR and IR T-ALL Girls: repeat 12 week cycles of maintenance for a total duration of 2 years from Interim Maintenance start.
- VHR T-ALL Girls: Repeat 12 week cycles of maintenance for a total duration of 2 years from Intensification Block 1 start.
- SR and IR T-ALL Boys: repeat 12 week cycles of maintenance for a total duration of 3 years from Interim Maintenance start.
- VHR T-ALL Boys: Repeat 12 week cycles of maintenance for a total duration of 3 years from Intensification Block 1 start.
- T-LLy regardless of gender: repeat 12 week cycles of maintenance for a total duration of 2 years from Interim Maintenance start.
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Pre-phase
Methylprednisolone monotherapy
back to top |
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
- Update: Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. Epub 2021 Jul 6. link to original article PubMed
Upfront induction therapy
Daunorubicin, Pegaspargase, Vincristine, Dexamethasone
back to top |
Regimen, modified ABFM
Study | Years of enrollment | Evidence |
---|---|---|
Vora et al. 2013 (UKALL 2003) | 2003-2011 | Non-randomized portion of RCT |
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 per day on days 4 & 18
- 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) 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
References
- UKALL 2003: Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. link to original article PubMed ISRCTN07355119
Daunorubicin, Pegaspargase, Vincristine, Prednisone
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Non-randomized portion of RCT |
Chemotherapy
- Daunorubicin (Cerubidine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
- Pegaspargase (Oncaspar) 2500 units/m2 IV once on day 5 +/- 1 day
- 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
4-week course
Subsequent treatment
- Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
DOLP
back to top |
DOLP: Daunorubicin, Oncovin (Vincristine), L-Asparaginase, Prednisone
DVPA: Daunorubicin, Vincristine, Prednisone, Asparaginase
Regimen (BFM 76/79 Phase I)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gaynon et al. 1988 (CCG-106) | 1983-1984 | Phase 3 (E-esc) | 1. Control regimen | Seems to have superior EFS36 |
2. New York regimen | Did not meet primary endpoint of EFS36 | |||
Steinherz et al. 1998 (CCG-123) | 1983-1985 | Phase 3 (C) | 1. LSA2-L2 & WBRT 2. LSA-L2 3. New York regimen |
Did not meet primary endpoint of EFS |
Note: the specific days of L-asparaginase are not specified; the schedule here is similar to those of other similar protocols.
Chemotherapy
- Daunorubicin (Cerubidine) 25 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
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 28, then tapered over 2 weeks
CNS therapy
- Methotrexate (MTX) IT once per day on days 1, 15, 29 (dose not specified)
6-week course
Subsequent treatment
- BFM 76/79 Phase II
References
- CCG-106: Gaynon PS, Steinherz PG, Bleyer WA, Ablin AR, Albo VC, Finklestein JZ, Grossman NJ, Littman PS, Novak LT, Pyesmany AF, Sather HN, Hammond GD. Intensive therapy for children with acute lymphoblastic leukaemia and unfavourable presenting features: early conclusions of study CCG-106 by the Childrens Cancer Study Group. Lancet. 1988 Oct 22;2(8617):921-4. link to original article PubMed
- CCG-123: Steinherz PG, Gaynon PS, Breneman JC, Cherlow JM, Grossman NJ, Kersey JH, Johnstone HS, Sather HN, Trigg ME, Uckun FM, Bleyer WA. Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group. Cancer. 1998 Feb 1;82(3):600-12. link to original article contains verified protocol PubMed
Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Place et al. 2015 (DFCI 05-001) | 2005-2011 | Phase 3 (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 3 (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
- Update: Vrooman LM, Blonquist TM, Stevenson KE, Supko JG, Hunt SK, Cronholm SM, Koch V, Kay-Green S, Athale UH, Clavell LA, Cole PD, Harris MH, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Place AE, Schorin MA, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. J Clin Oncol. 2021 Nov 1;39(31):3496-3505. Epub 2021 Jul 6. link to original article PubMed
Consolidation after upfront therapy
Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (E-esc) | Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 8 & 50
- Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
- Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
- Nelarabine (Arranon) 650 mg/m2 IV once per day on days 1 to 5, 43 to 47
- Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 22 & 64
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 22, 64, 71
CNS prophylaxis
- Methotrexate (MTX) (dose not specified) IT on days 15, 22, 57, 64
- Whole-brain irradiation in some arms (see paper for details)
71-day course
Subsequent treatment
- Interim maintenance; see paper for details
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine
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Regimen variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (C) | Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine | Not reported | Similar toxicity |
Note: although the induction doses of vincristine are capped at 2 mg, capping is not mentioned in the subsequent phases of treatment.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 8 & 50
- Cytarabine (Ara-C) 75 mg/m2 IV or SC once per day on days 8 to 11, 15 to 18, 50 to 53, 57 to 60
- Mercaptopurine (6-MP) 60 mg/m2 PO once per day on days 8 to 21, 50 to 63
- Pegaspargase (Oncaspar) 2500 units/m2 IM once per day on days 22 & 64
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 22, 64, 71
CNS prophylaxis
- Methotrexate (MTX) (dose not specified) IT on days 15, 22, 57, 64
- Whole-brain irradiation in some arms (see paper for details)
71-day course
Subsequent treatment
- Interim maintenance; see paper for details
Regimen variant #2
Study | Years of enrollment | Evidence |
---|---|---|
(COG AALL1231) | 2014-NR | Non-randomized portion of RCT |
Note: this regimen is available as a COG protocol but no manuscript has been published yet, to our knowledge. Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 30 to 60 minutes 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
- Dose may be modified based on TPMT status
- Pegaspargase (Oncaspar) 2500 units/m2 IV over 1 to 2 hours 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
Supportive medications
- Mesna (Mesnex) "is not required for this dose of cyclophosphamide, but may be administered at institutional discretion."
CNS prophylaxis
- Methotrexate (MTX) as follows, for CNS3:
- Ages 1 to 1.99: 8 mg IT once per day on days 1 & 8
- Ages 2 to 2.99: 10 mg IT once per day on days 1 & 8
- Ages 3 to 8.99: 12 mg IT once per day on days 1 & 8
- Age 9 and older: 15 mg IT once per day on days 1 & 8
50-day course
Subsequent treatment
- See protocol for details of treatment beyond consolidation, which is guided by MRD status obtained at the end of induction.
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
- COG AALL1231: NCT02112916
Doxorubicin, L-asparaginase, Mercaptopurine, Vincristine, Prednisone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Asselin et al. 2011 (POG 9404) | 1996-2001 | Phase 3 (C) | Doxorubicin, L-asparaginase, Mercaptopurine, Methotrexate, Vincristine, Prednisone | Seems to have inferior EFS |
Chemotherapy
- Doxorubicin (Adriamycin)
- Asparaginase (Elspar)
- Mercaptopurine (6-MP)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
References
- POG 9404: Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchison R, Lipshultz SE, Camitta BM. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood. 2011 Jul 28;118(4):874-83. Epub 2011 Apr 7. link to original article link to PMC article PubMed
Doxorubicin, L-asparaginase, Mercaptopurine, Methotrexate, Vincristine, Prednisone
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Asselin et al. 2011 (POG 9404) | 1996-2001 | Phase 3 (E-esc) | Doxorubicin, L-asparaginase, Mercaptopurine, Vincristine, Prednisone | Seems to have superior EFS |
Chemotherapy
- Doxorubicin (Adriamycin)
- Asparaginase (Elspar)
- Mercaptopurine (6-MP)
- Methotrexate (MTX)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
References
- POG 9404: Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchison R, Lipshultz SE, Camitta BM. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood. 2011 Jul 28;118(4):874-83. Epub 2011 Apr 7. link to original article link to PMC article PubMed
Etoposide & TBI, then allo HSCT
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
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
- 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
- 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-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
- 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-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
L-asparaginase monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Amylon et al. 1999 (POG 8704) | 1987-1992 | Phase 3 (E-esc) | No L-asp | Superior CRR |
Chemotherapy
- Asparaginase (Elspar) 25,000 units/m2 IM once per day on days 1, 8, 15, 22
28-day cycle for 5 cycles
References
- POG 8704: Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M, Katz J, Yu A, Laver J, Ravindranath Y, Kurtzberg J, Desai S, Camitta B, Murphy SB. Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study. Leukemia. 1999 Mar;13(3):335-42. link to original article contains protocol PubMed
Interim maintenance
Mercaptopurine, Methotrexate, Vincristine
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BFM HDMTX: Berlin Frankfurt Muenster High-Dose MTX (Methotrexate) regimen
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (C) | COG C-MTX | Seems to have inferior OS1 |
1Reported efficacy is based on the 2018 update.
Details to be completed
Preceding treatment
- Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine induction
Chemotherapy
8-week course
Subsequent treatment
- Delayed intensification
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Methotrexate, Pegaspargase, Vincristine
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COG C-MTX: Children's Oncology Group Capizzi-style MTX (Methotrexate) regimen
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winter et al. 2015 (COG AALL0434) | 2007-2014 | Phase 3 (C) | BFM HDMTX | Seems to have superior OS |
Details to be completed; reported efficacy is based on the 2018 update.
Preceding treatment
- Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine versus Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine induction
Chemotherapy
8-week course
Subsequent treatment
- Delayed intensification
References
- COG AALL0434: Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, Leonard Rn MS, Murphy J, Gastier-Foster JM, Carroll AJ, Heerema NA, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015 Jul;62(7):1176-83. Epub 2015 Mar 8. link to original article link to PMC article contains verified protocol PubMed NCT00408005
- Update: Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. Epub 2018 Aug 23. link to original article link to PMC article PubMed
- Update: Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. Epub 2020 Aug 19. link to original article link to PMC article PubMed
Relapsed or refractory
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-NR | Phase 3, <20 pts in this subgroup (E-switch-ic) | Idarubicin, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone | Did not meet primary endpoint of PFS |
Note: per the protocol, this regimen is intended only for patients 18 and younger and for patients allergic to pegaspargase. This is the same regimen used in relapsed B-ALL, but this subgroup did not have a statistically significant difference between the regimens.
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 ISRCTN45724312
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-NR | Phase 3, <20 pts in this subgroup (E-switch-ic) | Idarubicin, Pegaspargase, Vincristine, Dexamethasone | Did not meet primary endpoint of PFS |
Note: per the protocol, this regimen is intended only for patients 18 and younger. This is the same regimen used in relapsed B-ALL, but this subgroup did not have a statistically significant difference between the regimens.
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 ISRCTN45724312
Nelarabine monotherapy
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Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Berg et al. 2005 | 1997-2002 | Phase II (RT) | ORR: 14-55% |
Zwaan et al. 2017 (GSK 111081) | 2009-2014 | Phase IV | ORR: 39% |
Chemotherapy
- Nelarabine (Arranon) 650 mg/m2 IV over 60 minutes once per day on days 1 to 5
21-day cycles
References
- Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, Billett A, Kurtzberg J, Reaman G, Gaynon P, Whitlock J, Krailo M, Harris MB; Children's Oncology Group. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005 May 20;23(15):3376-82. link to original article contains protocol PubMed
- GSK 111081: Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, Ranganathan S, Leverger G. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017 Oct;179(2):284-293. Epub 2017 Aug 2. link to original article contains verified protocol PubMed NCT00866671