Anaplastic large cell lymphoma, pediatric

Section editor
	David Noyd, MD, MPH University of Washington Seattle, WA, USA LinkedIn

This page contains studies that were specific to pediatric populations. For the more general ALCL page, follow this link.

3 regimens on this page 5 variants on this page

Untreated

COG ANHL12P1 protocol

Study	Dates of enrollment	Evidence
Lowe et al. 2021 (COG ANHL12P1)	2013-2017	Randomized Phase 2

Note: there appear to be several dosing errors in Table 2; the authors have been contacted for clarification.

Pre-phase

Chemotherapy

• Cyclophosphamide (Cytoxan) 200 mg/m² IV once per day on days 1 & 2

Glucocorticoid therapy

• Dexamethasone (Decadron) 5 mg/m²/day PO on days 1 & 2, then 10 mg/m²/day PO on days 3 to 5

CNS therapy, prophylaxis

• Methotrexate (MTX) age-based IT once on day 1

5-day course

Induction

Antibody-drug conjugate therapy

• Brentuximab vedotin (Adcetris) 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1

Chemotherapy

• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1
• Ifosfamide (Ifex) as follows:
  • Cycles 1, 3, 5: 800 mg/m² IV once per day on days 1 to 5
• Etoposide (Vepesid) as follows:
  • Cycles 1, 3, 5: 100 mg/m² IV once per day on days 4 & 5
• Cytarabine (Ara-C) as follows:
  • Cycles 1, 3, 5: 150 mg/m² IV every 12 hours on days 4 & 5 (total dose per cycle: 600 mg/m²)
• Cyclophosphamide (Cytoxan) as follows:
  • Cycles 2, 4, 6: 200 mg/m² IV once per day on days 1 to 5
• Doxorubicin (Adriamycin) as follows:
  • Cycles 2, 4, 6: 25 mg/m² IV once per day on days 4 & 5

Glucocorticoid therapy

• Dexamethasone (Decadron) 10 mg/m²/day PO on days 1 to 5

21-day cycle for 6 cycles

References

1. COG ANHL12P1: Lowe EJ, Reilly AF, Lim MS, Gross TG, Saguilig L, Barkauskas DA, Wu R, Alexander S, Bollard CM. Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1. Blood. 2021 Jul 1;137(26):3595-3603. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01979536

EICNHL ALCL99 protocol

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Brugières et al. 2009 (EICNHL ALCL99)	1999-2005	Randomized (E-switch-ic)	EICHNL ALCL99; alternate MTX dosing	Inconclusive whether non-inferior EFS (primary endpoint)	Less toxic

Note: the intrathecal component is only described as "triple therapy" in the manuscript.

Pre-phase

Chemotherapy

• Cyclophosphamide (Cytoxan) 200 mg/m² IV once per day on days 1 & 2

Glucocorticoid therapy

• Dexamethasone (Decadron) 5 mg/m²/day PO on days 1 & 2, then 10 mg/m²/day PO on days 3 to 5

CNS therapy, prophylaxis

• Methotrexate (MTX) (dose not specified) IT once on day 1
• Cytarabine (Ara-C) (dose not specified) IT once on day 1
• Hydrocortisone (Cortef) (dose not specified) IT once on day 1

5-day course

Induction

Chemotherapy

• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1
• Ifosfamide (Ifex) as follows:
  • Cycles 1, 3, 5: 800 mg/m² IV once per day on days 1 to 5
• Etoposide (Vepesid) as follows:
  • Cycles 1, 3, 5: 100 mg/m² IV once per day on days 4 & 5
• Cytarabine (Ara-C) as follows:
  • Cycles 1, 3, 5: 150 mg/m² IV every 12 hours on days 4 & 5 (total dose per cycle: 600 mg/m²)
• Cyclophosphamide (Cytoxan) as follows:
  • Cycles 2, 4, 6: 200 mg/m² IV once per day on days 1 to 5
• Doxorubicin (Adriamycin) as follows:
  • Cycles 2, 4, 6: 25 mg/m² IV once per day on days 4 & 5

Glucocorticoid therapy

• Dexamethasone (Decadron) 10 mg/m²/day PO on days 1 to 5

21-day cycle for 6 cycles

References

1. EICNHL ALCL99: Brugières L, Le Deley MC, Rosolen A, Williams D, Horibe K, Wrobel G, Mann G, Zsiros J, Uyttebroeck A, Marky I, Lamant L, Reiter A. Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group. J Clin Oncol. 2009 Feb 20;27(6):897-903. Epub 2009 Jan 12. link to original article contains dosing details in manuscript PubMed NCT00006455

APO

APO: Adriamycin (Doxorubicin), Prednisone, Oncovin (Vincristine)
HOP: Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study	Dates of enrollment	Evidence
Alexander et al. 2014 (COG ANHL0131)	2004-2008	Non-randomized part of phase 3 RCT

Chemotherapy

• Doxorubicin (Adriamycin) 75 mg/m² IV once per day on days 1 & 22
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m²/day PO on days 1 to 28

CNS therapy, prophylaxis

• Methotrexate (MTX) age-adjusted IT once per day on days 1, 8, 22

6-week course

Subsequent treatment

• APO versus APV maintenance

References

1. COG ANHL0131: Alexander S, Kraveka JM, Weitzman S, Lowe E, Smith L, Lynch JC, Chang M, Kinney MC, Perkins SL, Laver J, Gross TG, Weinstein H. Advanced stage anaplastic large cell lymphoma in children and adolescents: results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: a report from the children's oncology group. Pediatr Blood Cancer. 2014 Dec;61(12):2236-42. Epub 2014 Aug 23. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00059839

Relapsed or refractory, subsequent lines of therapy

Crizotinib monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Mossé et al. 2013 (COG ADVL0912)	2009-2012	Phase 1/2 (RT)

Note: this was an expansion cohort of a phase 1/2 study.

Biomarker eligibility criteria

• ALK rearrangement

Targeted therapy

• Crizotinib (Xalkori) 280 mg/m² PO twice per day on days 1 to 28

28-day cycles

References

1. COG ADVL0912: Mossé YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, Rolland D, Balis FM, Maris JM, Weigel BJ, Ingle AM, Ahern C, Adamson PC, Blaney SM. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol. 2013 May;14(6):472-80. Epub 2013 Apr 16. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00939770