Treatment of Acute Lymphoblastic Leukemia in Children

NCT00165178 | Completed Phase 3 DMC

• 1 other identifier: 00-001
• Study Type: interventional
• Target: 498
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to reduce the side-effects from anti-leukemia therapy. The therapy in this study is based upon treatment information learned from prior clinical research programs as well as from laboratory research.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute lymphoblastic leukemia in children; High Risk ALL; Standard Risk ALL; E. coli asparaginase

Outcome Measures

Primary Outcomes (2)

• To optimize dosing of E. coli L-asparaginase during the intensification period

  5 years

• To determine the side effects of prednisone versus dexamethasone.

  5 years

Secondary Outcomes (1)

• To compare randomized treatment groups using health-related, quality-of-life analysis

  5 years

Study Arms (4)

Individualized ASP dose

EXPERIMENTAL

Drug: doxorubicin; Drug: E. coli asparaginase; Drug: vincristine; Drug: methotrexate; Drug: Leucovorin; Drug: cytarabine; Drug: Methotrexate/Hydrocortisone

Fixed dose ASP

ACTIVE COMPARATOR

Drug: doxorubicin; Drug: E. coli asparaginase; Drug: vincristine; Drug: methotrexate; Drug: Leucovorin; Drug: cytarabine; Drug: Methotrexate/Hydrocortisone

Dexamethasone

EXPERIMENTAL

Drug: dexamethasone; Drug: doxorubicin; Drug: vincristine; Drug: methotrexate; Drug: Leucovorin; Drug: Asparaginase; Drug: cytarabine; Drug: Methotrexate/Hydrocortisone

Prednisone

ACTIVE COMPARATOR

Drug: prednisone; Drug: doxorubicin; Drug: vincristine; Drug: methotrexate; Drug: Leucovorin; Drug: Asparaginase; Drug: cytarabine; Drug: Methotrexate/Hydrocortisone

Interventions

prednisone DRUG

Induction Phase: Given orally or intravenously Days 0-28 Intensification Phase: Given orally Days 1-5 of each cycle Continuation Phase: Given orally Days 1-5 of each cycle

Prednisone

dexamethasone DRUG

Intensification Phase: Given orally days 1-5 of each cycle Continuation Phase: Given orally days 1-5 pf each cycle

Dexamethasone

doxorubicin DRUG

Induction Phase: Intravenously on Days 0,1 Intensification Phase: Intravenously on Day 1 of each cycle

Also known as: dexrazoxane

Dexamethasone; Fixed dose ASP; Individualized ASP dose; Prednisone

E. coli asparaginase DRUG

Intensification Phase: In the muscle weekly. Dose will vary

Fixed dose ASP; Individualized ASP dose

vincristine DRUG

Induction: Intravenously on days 0, 7, 14, 21 MLL Intensification Phase: Intravenously on Days 1, 8, 15, 22 CNS Therapy: Intravenously on Day 1 Intensification Phase: Intravenously on day 1 of each cycle Continuation Phase: Intravenously on Day 1 of each cycle

Dexamethasone; Fixed dose ASP; Individualized ASP dose; Prednisone

methotrexate DRUG

Induction: Intravenously on Day 2 MLL Intensification: Intravenously on Days 1, 8 Intensification: (when doxorubicin completed) Intravenously or into the muscle weekly Continuation: Intravenously or into the muscle weekly

Dexamethasone; Fixed dose ASP; Individualized ASP dose; Prednisone

Leucovorin DRUG

Induction Phase: Intravenously or orally begins 36 hours after methotrexate MLL Intensification: Intravenously or orally begins 36 hours after methotrexate

Dexamethasone; Fixed dose ASP; Individualized ASP dose; Prednisone

Asparaginase DRUG

Induction: Into the muscle on Day 4 MLL Intensification: Into the muscle on Days 16, 23

Dexamethasone; Prednisone

cytarabine DRUG

Induction: Intrathecal on Days 0, 14, 28 MLL Intensification: Intravenously on Days 15, 16, 22, 23

Also known as: ARA-C

Dexamethasone; Fixed dose ASP; Individualized ASP dose; Prednisone

Methotrexate/Hydrocortisone DRUG

Induction: Intrathecal on Days 14, 28 MLL Intensification: Intrathecal on Days 2,9

Dexamethasone; Fixed dose ASP; Individualized ASP dose; Prednisone

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Acute lymphoblastic leukemia excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14) (q24;q32), t(8;22) or t(2;8)
• Age \> 12 months but less than 18 years

You may not qualify if:

• Prior therapy except, 1 week of steroids, or emergent radiation therapy to the mediastinum
• Known HIV positive

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Boston Children's Hospital: collaborator
• University of Rochester: collaborator
• McMaster University: collaborator
• San Jorge Children's Hospital (Puerto Rico): collaborator
• St. Justine's Hospital: collaborator
• Maine Children's Cancer Program: collaborator
• Ochsner Health System: collaborator
• Tulane University School of Medicine: collaborator
• Laval University: collaborator
• Columbia University: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (5)

• Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Arkin S, Declerck L, Cohen HJ, Sallan SE. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood. 2001 Mar 1;97(5):1211-8. doi: 10.1182/blood.v97.5.1211.

  PMID: 11222362 BACKGROUND

• Silverman LB, Declerck L, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Lipton JM, Cohen HJ, Sallan SE. Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995). Leukemia. 2000 Dec;14(12):2247-56. doi: 10.1038/sj.leu.2401980.

  PMID: 11187916 BACKGROUND

• Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L, Cohen HJ, Sallan SE, Asselin BL. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol. 2003 Oct 1;21(19):3616-22. doi: 10.1200/JCO.2003.10.116.

  PMID: 14512392 BACKGROUND

• Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, Colan SD, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Gelber RD, Sallan SE. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med. 2004 Jul 8;351(2):145-53. doi: 10.1056/NEJMoa035153.

  PMID: 15247354 BACKGROUND

• Vrooman LM, Stevenson KE, Supko JG, O'Brien J, Dahlberg SE, Asselin BL, Athale UH, Clavell LA, Kelly KM, Kutok JL, Laverdiere C, Lipshultz SE, Michon B, Schorin M, Relling MV, Cohen HJ, Neuberg DS, Sallan SE, Silverman LB. Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study--Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013 Mar 20;31(9):1202-10. doi: 10.1200/JCO.2012.43.2070. Epub 2013 Jan 28.

  PMID: 23358966 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Prednisone; Dexamethasone; Doxorubicin; Dexrazoxane; Vincristine; Methotrexate; Leucovorin; Asparaginase; Cytarabine; Hydrocortisone

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes; Amidohydrolases; Hydrolases; Enzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Lewis Silverman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: September 1, 2000
• Primary Completion: December 1, 2004
• Study Completion: May 1, 2011
• Last Updated: April 25, 2013

Record last verified: 2013-04

Locations

US (1)