Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more cancer cells. It is not yet known which regimen of combination chemotherapy is more effective for acute lymphoblastic leukemia PURPOSE: Randomized phase III trial to compare different regimens of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.

Timeline

Start

1996-05

Primary completion

2007-03

Completion

2007-03

Outcome

Mixed primary results

paper The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (+/- 1.8%) and to MP was 79.0% (+/- 2.1%; P = .004 log rank) PMID 20124218 ↗

paper Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). PMID 16609069 ↗

Publications

• Background Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008 Dec;22(12):2142-50. doi: 10.1038/leu.2008.251. Epub 2008 Sep 25.
• Background Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.
• Results Stork LC, Matloub Y, Broxson E, La M, Yanofsky R, Sather H, Hutchinson R, Heerema NA, Sorrell AD, Masterson M, Bleyer A, Gaynon PS. Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial. Blood. 2010 Apr 8;115(14):2740-8. doi: 10.1182/blood-2009-07-230656. Epub 2010 Feb 1.
• Results Kadan-Lottick NS, Brouwers P, Breiger D, Kaleita T, Dziura J, Northrup V, Chen L, Nicoletti M, Bostrom B, Stork L, Neglia JP. Comparison of neurocognitive functioning in children previously randomly assigned to intrathecal methotrexate compared with triple intrathecal therapy for the treatment of childhood acute lymphoblastic leukemia. J Clin Oncol. 2009 Dec 10;27(35):5986-92. doi: 10.1200/JCO.2009.23.5408. Epub 2009 Nov 2.
• Results Malempati S, Gaynon PS, Sather H, La MK, Stork LC; Children's Oncology Group. Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Children's Oncology Group study CCG-1952. J Clin Oncol. 2007 Dec 20;25(36):5800-7. doi: 10.1200/JCO.2007.10.7508.
• Results Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC; Children's Oncology Group. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. Blood. 2006 Aug 15;108(4):1165-73. doi: 10.1182/blood-2005-12-011809. Epub 2006 Apr 11.
• Results Bassal M, La MK, Whitlock JA, Sather HN, Heerema NA, Gaynon PS, Stork LC. Lymphoblast biology and outcome among children with Down syndrome and ALL treated on CCG-1952. Pediatr Blood Cancer. 2005 Jan;44(1):21-8. doi: 10.1002/pbc.20193.
• Results Malempati S, Gaynon PS, Sather H, et al.: Outcome after relapse among children with standard risk (SR) ALL treated on CCG-1952. [Abstract] Blood 104 (11): A-520, 2004.
• Results Stork LC, Sather H, Hutchinson RJ, et al.: Comparison of mercaptopurine (MP) with thioguanine (TG) and IT methotrexate (ITM) with IT "triples" (ITT) in children with SR-ALL: results of CCG-1952. [Abstract] Blood 100 (11 Pt 1): A-585, 156a, 2002.
• Results Stork LC, Sather H, Yanofsky R, et al.: Hyperdiploidy with trisomy 10 and TEL-AML1 expression among children with standard risk acute lymphoblastic leukemia (SR-ALL): a CCG-1952 report. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1476, 2001.
• Results Gaynon PS, Stork L, Sather H, et al.: Leukemic progenitor cell content of pre- and post-induction chemotherapy bone marrow specimens from children with newly diagnosed or relapsed acute lymphoblastic leukemia (ALL). [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-2187, 567a, 1999.
• Results Stork LC, Erdmann G, Adamson P, et al.: Oral 6-thioguanine causes relatively mild and reversible hepatic veno-occlusive disease(VOD). J Pediatr Hematol Oncol 20: 400a, 1998.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cytarabine	Small molecule	—	Intrathecal
Subject	Hydrocortisone	Other / unclassified	—	—
Subject	MERCAPTOPURINE ANHYDROUS	Small molecule	—	Oral
Subject	Methotrexate	Small molecule	—	Intrathecal
Subject	Thioguanine	Small molecule	50 mg/m2	Oral
Subject	Thioguanine	Small molecule	60 mg/m2	Oral
Background	Cyclophosphamide	Other / unclassified	—	Intravenous
Background	Daunorubicin	Small molecule	—	Intravenous
Background	Dexamethasone	Small molecule	—	Oral
Background	Doxorubicin	Other / unclassified	—	Intravenous
Background	Pegaspargase	Protein / enzyme biologic	—	—
Background	Prednisone	Other / unclassified	—	Oral
Background	Vincristine	Small molecule	—	Intravenous
Background	asparaginase	Protein / enzyme biologic	—	Intramuscular

Indications