Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

Summary

This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Chemotherapy drugs, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Timeline

Start

2012-02-29

Primary completion

2022-12-31

Completion

2026-03-31

Outcome

Missed primary endpoint

paper Postinduction CNS prophylaxis with ITT did not improve 5-year DFS for children with HR B-ALL. PMID 32496902 ↗

registry analysis (superiority test); Non-DS VHR B-ALL Control Arm vs Non-DS VHR B-ALL Exp Arm1; p = 0.556; Hazard Ratio (HR) 1.019; Log Rank NCT02883049 ↗

Publications

• Chang TC, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen IM, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui CH, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia. J Clin Oncol. 2024 Oct 10;42(29):3491-3503. doi: 10.1200/JCO.23.02238. Epub 2024 Aug 9.
• Rabin KR, Devidas M, Chen Z, Ji L, Kairalla J, Hitzler JK, Yang JJ, Carroll AJ, Heerema NA, Borowitz MJ, Wood BL, Roberts KG, Mullighan CG, Harvey RC, Chen IM, Willman CL, Reshmi SC, Gastier-Foster JM, Bhojwani D, Rheingold SR, Maloney KW, Mattano LA, Larsen EC, Schore RJ, Burke MJ, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Angiolillo AL. Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group. J Clin Oncol. 2024 Jan 10;42(2):218-227. doi: 10.1200/JCO.23.00389. Epub 2023 Oct 27.
• Salzer WL, Burke MJ, Devidas M, Dai Y, Hardy KK, Kairalla JA, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131. J Clin Oncol. 2020 Aug 10;38(23):2628-2638. doi: 10.1200/JCO.19.02892. Epub 2020 Jun 4.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Clofarabine	Other / unclassified	—	Intravenous
Subject	Cyclophosphamide	Other / unclassified	—	Intravenous
Subject	Cytarabine	Small molecule	—	Intrathecal
Subject	Etoposide	Small molecule	—	Intravenous
Subject	Hydrocortisone	Other / unclassified	—	Intrathecal
Subject	Methotrexate	Small molecule	—	Intrathecal
Subject	dasatinib anhydrous	Small molecule	—	Oral
Background	Daunorubicin	Small molecule	—	Intravenous
Background	Dexamethasone	Small molecule	—	Oral
Background	Doxorubicin	Other / unclassified	—	Intravenous
Background	Leucovorin	Small molecule	—	Oral
Background	MERCAPTOPURINE ANHYDROUS	Small molecule	—	Oral
Background	Pegaspargase	Protein / enzyme biologic	—	Intravenous
Background	Prednisone	Other / unclassified	—	Oral
Background	Thioguanine	Small molecule	—	Oral
Background	Vincristine	Small molecule	—	Intravenous

Indications