T-cell acute lymphoblastic leukemia, pediatric

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 David Noyd, MD, MPH
University of Washington
Seattle, WA, USA
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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


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

Upfront therapy

COG AALL0434 protocol

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Winter et al. 2015 (COG AALL0434) 2007-2014 Phase 3 (E-RT-esc) Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine Seems to have superior DFS1 (primary endpoint) Similar toxicity

1Reported efficacy is based on the 2020 update.

Induction, Arms B (Nelarabine Arms)

All Patients

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Age in years, rounded to the nearest hundredth Initial Dose
1.00 to 1.99 30 mg
2.00 to 2.99 50 mg
3.00 or older 70 mg
Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

29-day course


Consolidation, Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, Pegaspargase, Vincristine

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 over 30 minutes on days 8, 50
    • Must reduce urine specific gravity to less than or equal to 1.015 prior to administration
  • Cytarabine (Ara-C) 75 mg/m2 IV over 1 to 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 to 2 hours once per day on days 22 & 64
  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 22, 29, 64, 71

CNS therapy, prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg
  • Whole-brain irradiation by the following risk-based criteria:
    • 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

Interim Maintenance, with Capizzi MTX (Arms A and B)

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

  • 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 to 2 hours once per day on days 2, 22

CNS therapy, prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Delayed Intensification, Nelarabine Arms (Arms B and D)

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

Radiotherapy

  • Total body irradiation (TBI) by the following risk-based criteria:
    • Arm D Only: 1,200 cGy in 8 once daily fractions to start on day 50 of DI
    • CNS3 T-ALL: 1,800 cGy in 10 once daily fractions to start on day 50 of DI

63-day course


Maintenance, Arms B and D

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) on days 1, 57
  • Mercaptopurine (6-MP) 75 mg/m2 PO once per day on days 1 to 28, 36 to 84
  • Methotrexate (MTX) 20 mg/m2 PO on days 8, 15, 22, 36, 43, 50, 57, 64, 71, 78
    • No dose escalation recommended for the first maintenance cycle
    • Thereafter, for ANC at least 1500 μL 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 to 33
    • DO NOT Administer with other Chemotherapy agents

Glucocorticoid therapy

  • Prednisone (Sterapred) 20 mg/m2 PO twice per day on days 1 to 5 and 57 to 61 (Total of 40 mg/m2/day, divided twice per day)

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg 
Repeat above cycle for a total of 3 cycles.

3 cycles


Maintenance, continuation after cycle 3 (Arms B and D)

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, 57
  • Mercaptopurine (6-MP) 75 mg/m2 PO once per day on days 1 to 84
  • Methotrexate (MTX) 20 mg/m2 PO once per day on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
    • No dose escalation recommended for the first maintenance cycle
    • Thereafter, for ANC at least 1500 μL on 3 CBCs done over 6 weeks or 2 monthly CBCs, increase dose of methotrexate or mercaptopurine by 25%

Glucocorticoid therapy

  • Prednisone (Sterapred) 20 mg/m2 PO twice per day on days 1 to 5, 29 to 33, 57 to 61 (Total of 40 mg/m2/day, divided twice per day)

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 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

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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 Protocol Arm A

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Teachey et al. 2022 (COG AALL1231) 2014-2017 Phase 3 (C) COG AALL1231 Protocol Arm B (with bortezomib) Did not meet primary endpoint of EFS

Note: Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.

Induction

All T-ALL and T-LLy patients

Chemotherapy

Glucocorticoid therapy

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 in years, rounded to the nearest hundredth Initial Dose
1.00 to 1.99 30 mg
2.00 to 2.99 50 mg
3.00 or older 70 mg

CNS treatment

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

Consolidation

All T-ALL and T-LLy Patients

Chemotherapy

CNS prophylaxis

  • Methotrexate (MTX) IT once per day on days 1, 8, 15, 22
    • CNS3 patients and CNS3 T-LLy: Omit days 15, 22
Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Interim Maintenance, SR patients, with CMTX

SR Patients Receive After Consolidation

Chemotherapy

  • Methotrexate (MTX) 100 mg/m2 IV once on day 1, then 150 mg/m2 IV once on day 11, then 200 mg/m2 IV once on day 21, then 250 mg/m2 IV once on day 31, then 300 mg/m2 IV once on day 41
    • 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 IV over 1 to 2 hours once per day on days 2, 22

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Delayed Intensification

All T-ALL and T-LLy Patients

Chemotherapy

Glucocorticoid therapy

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Delayed Intensification, IR patients

All T-ALL and T-LLy Patients

Chemotherapy

Glucocorticoid therapy

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Interim Maintenance, #1 with HDMTX - ALL IR Patients

SR and VHR T-ALL and T-LLy DO NOT RECEIVE

Chemotherapy

Supportive therapy

  • Leucovorin (Folinic acid) 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, 45, 46

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Interim Maintenance, #2 with CMTX - ALL IR Patients

IR T-ALL and T-LLy Patients receive this after DI as IM#2

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 IV over 1 to 2 hours once per day on days 2, 22

CNS prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Intensification, Block 1 (VHR patients)

VHR Patients receive immediately after consolidation

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • Leucovorin (Folinic acid) 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
  • Filgrastim (Neupogen) 5 mcg/kg SC or IV once per day beginning on day 7 and until WBC count more than 3 x 109/L

CNS prophylaxis, Triple Intrathecal Therapy

  • Methotrexate (MTX) by the following age-based criteria:
    • 1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
  • Hydrocortisone (Cortef) by the following age-based criteria:
    • 1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
  • Cytarabine (Ara-C) by the following age-based criteria:
    • 1 up to 2 years old: 16 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 20 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 24 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 30 mg IT on day 1, given 2 hours after the start of HD MTX infusion

Intensification, Block 2

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • Leucovorin (Folinic acid) 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
  • Mesna (Mesnex) 300 mg/m2 at hour 0, 4, and 8 from the start of each ifosfamide infusion on days 2 to 4
  • Filgrastim (Neupogen) 5 mcg/kg SC or IV once per day beginning on day 7 and until WBC count more than 3 x 109/L

CNS prophylaxis, Triple Intrathecal Therapy

  • Methotrexate (MTX) by the following age-based criteria:
    • 1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
  • Hydrocortisone (Cortef) by the following age-based criteria:
    • 1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
  • Cytarabine (Ara-C) by the following age-based criteria:
    • 1 up to 2 years old: 16 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 20 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 24 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 30 mg IT on day 1, given 2 hours after the start of HD MTX infusion

Intensification, Block 3

Chemotherapy

  • High Dose Cytarabine (Ara-C) 2,000 mg/m2 every 12 hours IV over 3 hours x 4 doses on days 1, 2
  • Etoposide (Vepesid) 100 mg/m2 every 12 hours IV over 1 to 2 hours x 5 doses on days 3 to 5
    • First dose to be given 12 hours after the start of the 4th high dose Cytarabine (Ara-C) on day 2
    • Infusion rate should not exceed 300 mg/m2/hour (10 mg/kg/hour)
  • Pegaspargase (Oncaspar) 2,500 units/m2 IV over 1 to 2 hours on day 6

Glucocorticoid therapy

Supportive therapy

CNS therapy, Triple Intrathecal Therapy

  • Methotrexate (MTX) by the following age-based criteria:
    • 1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
  • Hydrocortisone (Cortef) by the following age-based criteria:
    • 1 up to 2 years old: 8 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 10 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 12 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 15 mg IT on day 1, given 2 hours after the start of HD MTX infusion
  • Cytarabine (Ara-C) by the following age-based criteria:
    • 1 up to 2 years old: 16 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 2 up to 3 years old: 20 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 3 up to 9 years old: 24 mg IT on day 1, given 2 hours after the start of HD MTX infusion
    • 9 years old and older: 30 mg IT on day 1, given 2 hours after the start of HD MTX infusion

Delayed Intensification

All T-ALL and T-LLy Patients

Chemotherapy

Glucocorticoid therapy

  • Dexamethasone (Decadron) 5 mg/m2 IV or PO twice per day on days 1 to 7 and 15 to 21 (10 mg/m2/day, divided twice per day)

CNS therapy, prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Interim Maintenance, with CMTX

VHR Patients receive after DI

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 IV over 1 to 2 hours once per day on days 2, 22

CNS therapy, prophylaxis

Age in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

56-day course


Maintenance, all patients

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 29, 57
  • Mercaptopurine (6-MP) 75 mg/m2 PO once per day on days 1 to 84
  • Methotrexate (MTX) 20 mg/m2 once per day on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 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

Glucocorticoid therapy

  • Dexamethasone (Decadron) 3 mg/m2 IV or PO twice per day on days 1 to 5, 29 to 33, 57 to 61 (6 mg/m2/day, divided twice per day)

CNS therapy, 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 in years, rounded to the nearest hundredth Dose
1.00 to 1.99 8 mg
2.00 to 2.99 10 mg
3.00 to 8.99 12 mg
9.00 or older 15 mg

Radiotherapy

  • Total body irradiation (TBI) during the first cycle of maintenance, by the following histology- and risk-based criteria:
    • T-ALL AND CNS1 VHR: 1200 cGy
    • T-ALL AND CNS2 VHR: 1200 cGy
    • T-ALL AND CNS3 IR: 1800 cGy
    • T-ALL AND CNS3 VHR: 1800 cGy
    • T-LLy AND CNS3 IR: 1800 cGy
    • T-LLy AND CNS3 VHR: 1800 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

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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
  2. COG AALL1231: Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. Epub 2022 Mar 10. link to original article link to PMC article PubMed NCT02112916

Pre-phase

Methylprednisolone monotherapy

Regimen

Study Dates of enrollment Evidence
Place et al. 2015 (DFCI 05-001) 2005-2011 Non-randomized part of phase 3 RCT
Burns et al. 2020 (DFCI 11-001) 2012-2015 Non-randomized part of phase 3 RCT

Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001.

Glucocorticoid therapy

3-day course

Subsequent treatment

References

  1. 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
    1. 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 dosing details in supplement link to PMC article PubMed
  2. 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 dosing details in supplement link to PMC article PubMed NCT01574274
    1. 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, L-Asparaginase, Vincristine, Dexamethasone

Regimen, modified ABFM

Study Dates of enrollment Evidence
Sato et al. 2023 (ALL-T11) 2011-12-01 to 2017-11-30 Phase 2

Note: Day counts included a 7-day pre-phase, not shown here.

Chemotherapy

Glucocorticoid therapy

  • Dexamethasone (Decadron) by the following age-based criteria:
    • Younger than 10 years old: 10 mg/m2/day PO on days 8 to 28
    • 10 years old or older: 10 mg/m2/day PO on days 8 to 14, 22 to 28

CNS therapy, prophylaxis

  • Cytarabine (Ara-C) by the following age-based criteria:
    • Younger than 1 year old: 16 mg IT once per day on days 12 & 33
    • 1 to 1.99 years old: 20 mg IT once per day on days 12 & 33
    • 2 to 2.99 years old: 26 mg IT once per day on days 12 & 33
    • 3 years old or older: 30 mg IT once per day on days 12 & 33
  • Methotrexate (MTX) by the following age-based criteria:
    • Younger than 1 year old: 6 mg IT once per day on days 12 & 33
    • 1 to 1.99 years old: 8 mg IT once per day on days 12 & 33
    • 2 to 2.99 years old: 10 mg IT once per day on days 12 & 33
    • 3 years old or older: 12 mg IT once per day on days 12 & 33
  • [[Prednisolone (Millipred) by the following age-based criteria
    • Younger than 1 year old: 4 mg IT once per day on days 12 & 33
    • 1 to 1.99 years old: 6 mg IT once per day on days 12 & 33
    • 2 to 2.99 years old: 8 mg IT once per day on days 12 & 33
    • 3 years old or older: 10 mg IT once per day on days 12 & 33

4-week course

Subsequent treatment

  • See paper for details

References

  1. ALL-T11: Sato A, Hatta Y, Imai C, Oshima K, Okamoto Y, Deguchi T, Hashii Y, Fukushima T, Hori T, Kiyokawa N, Kato M, Saito S, Anami K, Sakamoto T, Kosaka Y, Suenobu S, Imamura T, Kada A, Saito AM, Manabe A, Kiyoi H, Matsumura I, Koh K, Watanabe A, Miyazaki Y, Horibe K. Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group. Lancet Haematol. 2023 Jun;10(6):e419-e432. Epub 2023 May 8. Erratum in: Lancet Haematol. 2023 Jun;10(6):e399. link to original article contains dosing details in supplement PubMed jRCTs041180145

Daunorubicin, Pegaspargase, Vincristine, Dexamethasone

Regimen, modified ABFM

Study Dates of enrollment Evidence
Vora et al. 2013 (UKALL 2003) 2003-2011 Non-randomized part of phase 2 RCT

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

  • Cytarabine (Ara-C) by the following age-based criteria:
    • 1 to 1.99 years old: 30 mg IT once on day 1
    • 2 to 2.99 years old: 50 mg IT once on day 1
    • 3 years old or older: 70 mg IT once on day 1
  • Methotrexate (MTX) by the following age-based criteria:
    • 1 to 1.99 years old: 8 mg IT once per day on days 8 & 29
    • 2 to 2.99 years old: 10 mg IT once per day on days 8 & 29
    • 3 to 8.99 years old: 12 mg IT once per day on days 8 & 29
    • 9 years old or older: 15 mg IT once per day on days 8 & 29

4-week course

Subsequent treatment

References

  1. 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. Epub 2013 Feb 7. link to original article PubMed ISRCTN07355119

Daunorubicin, Pegaspargase, Vincristine, Prednisone

Regimen

Study Dates of enrollment Evidence
Winter et al. 2015 (COG AALL0434) 2007-2014 Non-randomized part of phase 3 RCT

Chemotherapy

Glucocorticoid therapy

4-week course

Subsequent treatment

References

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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

DOLP: Daunorubicin, Oncovin (Vincristine), L-Asparaginase, Prednisone
DVPA: Daunorubicin, Vincristine, Prednisone, Asparaginase

Regimen, BFM 76/79 Phase I

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gaynon et al. 1988 (CCG-106) 1983-05 to 1984-11 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

Glucocorticoid therapy

CNS therapy

6-week course

Subsequent treatment

  • BFM 76/79 Phase II

References

  1. 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
  2. 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 dosing details in manuscript PubMed

Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone

Regimen

Study Dates 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

Glucocorticoid therapy

Supportive therapy

28-day course

CNS therapy, prophylaxis

Subsequent treatment

References

  1. 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
    1. 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 dosing details in supplement link to PMC article PubMed
  2. 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 dosing details in supplement link to PMC article PubMed NCT01574274
    1. 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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Winter et al. 2015 (COG AALL0434) 2007-2014 Phase 3 (E-RT-esc) Cyclophosphamide, Cytarabine, Mercaptopurine, Pegaspargase, Vincristine Seems to have superior DFS1 (primary endpoint) Similar toxicity

1Reported efficacy is based on the 2020 update.
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

CNS therapy, prophylaxis

71-day course

Subsequent treatment

  • Interim maintenance; see paper for details

References

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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

Regimen variant #1

Study Dates 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

CNS therapy, prophylaxis

71-day course

Subsequent treatment

  • Interim maintenance; see paper for details


Regimen variant #2

Study Dates of enrollment Evidence
Teachey et al. 2022 (COG AALL1231) 2014-2017 Non-randomized part of phase 3 RCT

Note: Per the protocol, it is intended only for patients greater than 1 and less than 31 years of age.

Preceding treatment

Chemotherapy

Supportive therapy

  • Mesna (Mesnex) "is not required for this dose of cyclophosphamide, but may be administered at institutional discretion."

CNS therapy, prophylaxis

  • Methotrexate (MTX) by the following age-based criteria, for CNS3:
    • 1 to 1.99 years old: 8 mg IT once per day on days 1 & 8
    • 2 to 2.99 years old: 10 mg IT once per day on days 1 & 8
    • 3 to 8.99 years old: 12 mg IT once per day on days 1 & 8
    • 9 years old or 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

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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
  2. COG AALL1231: Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. Epub 2022 Mar 10. link to original article link to PMC article PubMed NCT02112916

Doxorubicin, Mercaptopurine, Methotrexate, Vincristine, Prednisone

Regimen variant #1, high-dose MTX

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Asselin et al. 2011 (POG 9404) 1996-2001 Phase 3 (E-esc) Doxorubicin, Mercaptopurine, Methotrexate, Vincristine, Prednisone; low-dose MTX Seems to have superior EFS (primary endpoint)

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

  • Doxorubicin (Adriamycin) 30 mg/m2 (maximum dose of 60 mg) IV once per day on days 1, 2, 22
  • Mercaptopurine (6-MP) 50 mg/m2 (maximum dose of 100 mg) PO once per day on days 22 to 36
  • Methotrexate (MTX) 40 mg/m2 (maximum dose of 80 mg) (route not specified) once on day 2, given 8 to 24 hours after doxorubicin, then 500 mg/m2 (maximum dose of 1000 mg) IV over 30 minutes once on day 22, then 4500 mg/m2 (maximum dose of 9000 mg) IV continuous infusion over 23.5 hours
  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push once per week on days 1, 8, 15, 22

Glucocorticoid therapy

Supportive therapy

  • Dexrazoxane (Zinecard) 300 mg/m2 (maximum dose of 600 mg) IV once per day on days 1, 2, 22, given immediately before each dose of doxorubicin

42-day course


Regimen variant #2, low-dose MTX

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Asselin et al. 2011 (POG 9404) 1996-2001 Phase 3 (C) Doxorubicin, Mercaptopurine, Methotrexate, Vincristine, Prednisone; high-dose MTX Seems to have inferior EFS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • Dexrazoxane (Zinecard) 300 mg/m2 (maximum dose of 600 mg) IV once per day on days 1, 2, 22, given immediately before each dose of doxorubicin

42-day course

References

  1. 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 contains dosing details in manuscript PubMed

Etoposide & TBI, then allo HSCT

Regimen

Study Dates of enrollment Evidence
Peters et al. 2015 (ALL-SCT-BFM 2003) 2003-2011 Non-randomized

Chemotherapy

Radiotherapy

Immunotherapy

One course

References

  1. 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 dosing details in manuscript PubMed
    1. 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
  2. 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 dosing details in manuscript PubMed
    1. 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
  3. ALL-SCT-BFM-2003: Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. link to original article PubMed NCT01423747

L-asparaginase monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Amylon et al. 1999 (POG 8704) 1987-1992 Phase 3 (E-esc) No L-asp Superior CRR

Chemotherapy

7-day cycle for 20 cycles

References

  1. 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 dosing details in abstract PubMed

Interim maintenance

Mercaptopurine, Methotrexate, Vincristine

BFM HDMTX: Berlin Frankfurt Muenster High-Dose MTX (Methotrexate) regimen

Regimen

Study Dates 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

Chemotherapy

8-week course

Subsequent treatment

  • Delayed intensification

References

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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

COG C-MTX: Children's Oncology Group Capizzi-style MTX (Methotrexate) regimen

Regimen

Study Dates 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

Chemotherapy

8-week course

Subsequent treatment

  • Delayed intensification

References

  1. 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 dosing details in manuscript PubMed NCT00408005
    1. 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
    2. 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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Parker et al. 2010 (CCLG ALL R3) 2003-2007 Phase 3, fewer than 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

Glucocorticoid therapy

CNS therapy, prophylaxis

  • Methotrexate (MTX) by the following age-based criteria:
    • Younger than 2 years old: 8 mg IT once per day on days 1 & 8
    • Age 2: 10 mg IT once per day on days 1 & 8
    • Older than 2 years old: 12 mg IT once per day on days 1 & 8

4-week course

Subsequent treatment

  • See paper for details of treatment beyond induction

References

  1. 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 dosing details in manuscript link to PMC article PubMed NCT00967057

Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Parker et al. 2010 (CCLG ALL R3) 2003-2007 Phase 3, fewer than 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

Glucocorticoid therapy

CNS therapy, prophylaxis

  • Methotrexate (MTX) by the following age-based criteria:
    • Younger than 2 years old: 8 mg IT once per day on days 1 & 8
    • Age 2: 10 mg IT once per day on days 1 & 8
    • Older than 2 years old: 12 mg IT once per day on days 1 & 8

4-week course

Subsequent treatment

  • See paper for details of treatment beyond induction

References

  1. 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 dosing details in manuscript link to PMC article PubMed NCT00967057

Nelarabine monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
Berg et al. 2005 1997-2002 Phase 2 (RT) ORR: 14-55%
Zwaan et al. 2017 (GSK 111081) 2009-2014 Phase 4 ORR: 39%

Chemotherapy

21-day cycles

References

  1. 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 dosing details in abstract PubMed
  2. 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 dosing details in manuscript PubMed NCT00866671
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