Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

NCT00005603 | Completed Phase 3 DMC

• 4 other identifiers: 9906COG-P9906POG-9906CDR0000067722
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 20

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for acute lymphoblastic leukemia. PURPOSE: Phase III trial to determine the effectiveness of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

childhood acute lymphoblastic leukemia in remission; B-cell childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy

  To determine for patients at high risk for treatment failure if the augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy, on the basis of historical controls.

Interventions

asparaginase DRUG

cyclophosphamide DRUG

cytarabine DRUG

daunorubicin hydrochloride DRUG

dexamethasone DRUG

doxorubicin hydrochloride DRUG

mercaptopurine DRUG

methotrexate DRUG

prednisone DRUG

thioguanine DRUG

vincristine sulfate DRUG

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of B-cell precursor acute lymphoblastic leukemia * Registered on POG-9900 Classification Study * Registered within 7 days of documenting complete response after induction on day 29 or, if 2 more weeks of induction are required, no later than day 49 * Classified as high risk: * No simultaneous trisomy 4 and 10 * No TEL-AML1 gene * Meets criteria for 1 of the following: * Any age with WBC \> 100,000/mm\^3 * CNS and bone marrow evaluations required for those patients with WBC \> 100,000/mm\^3 who are within 24 months of initial diagnosis * Age over 12 (boys) or 16 (girls) * If younger, WBC must be 1 of the following: * Greater than 80,000/mm\^3 (for boys age 8 or girls age 12) * Greater than 60,000/mm\^3 (for boys age 9 or girls age 13) * Greater than 40,000/mm\^3 (for boys age 10 or girls age 14) * Greater than 20,000/mm\^3 (for boys age 11 or girls age 15) * At least one of the following: * CNS 3 disease (CSF WBC at least 5/microliter with blasts present) * Testicular leukemia * MLL gene rearrangements PATIENT CHARACTERISTICS: Age: * 1 to 21 Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * Not specified Renal: * Not specified Other: * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * See Disease Characteristics Endocrine therapy: * Not specified Radiotherapy: * Not specified Surgery: * Not specified Other: * See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (20)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94143-0128, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Saint Jude Midwest Affiliate

Peoria, Illinois, 61637, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Albert Einstein Clinical Cancer Center

The Bronx, New York, 10461, United States

Location

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Doernbecher Children's Hospital

Portland, Oregon, 97201-3098, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0361, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Related Publications (19)

• Chen IM, Harvey RC, Mullighan CG, Gastier-Foster J, Wharton W, Kang H, Borowitz MJ, Camitta BM, Carroll AJ, Devidas M, Pullen DJ, Payne-Turner D, Tasian SK, Reshmi S, Cottrell CE, Reaman GH, Bowman WP, Carroll WL, Loh ML, Winick NJ, Hunger SP, Willman CL. Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study. Blood. 2012 Apr 12;119(15):3512-22. doi: 10.1182/blood-2011-11-394221. Epub 2012 Feb 24.

  PMID: 22368272 BACKGROUND

• Rabin KR, Gramatges MM, Borowitz MJ, Palla SL, Shi X, Margolin JF, Zweidler-McKay PA. Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012 Sep;59(3):468-74. doi: 10.1002/pbc.23395. Epub 2011 Nov 18.

  PMID: 22102553 BACKGROUND

• Yang JJ, Cheng C, Yang W, Pei D, Cao X, Fan Y, Pounds SB, Neale G, Trevino LR, French D, Campana D, Downing JR, Evans WE, Pui CH, Devidas M, Bowman WP, Camitta BM, Willman CL, Davies SM, Borowitz MJ, Carroll WL, Hunger SP, Relling MV. Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA. 2009 Jan 28;301(4):393-403. doi: 10.1001/jama.2009.7.

  PMID: 19176441 BACKGROUND

• Borowitz MJ, Devidas M, Hunger SP, et al.: Prognostic signficance of end consolidation minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG). [Abstract] J Clin Oncol 26 (Suppl 15): A-10000, 2008.

  BACKGROUND

• Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, Linda S, Martin PL, Pullen DJ, Viswanatha D, Willman CL, Winick N, Camitta BM; Children's Oncology Group. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008 Jun 15;111(12):5477-85. doi: 10.1182/blood-2008-01-132837. Epub 2008 Apr 3.

  PMID: 18388178 BACKGROUND

• Davies SM, Borowitz MJ, Rosner GL, Ritz K, Devidas M, Winick N, Martin PL, Bowman P, Elliott J, Willman C, Das S, Cook EH, Relling MV. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 15;111(6):2984-90. doi: 10.1182/blood-2007-09-114082. Epub 2008 Jan 8.

  PMID: 18182569 BACKGROUND

• Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ, Chen IM, Atlas SR, Kang H, Ar K, Wilson CS, Wharton W, Murphy M, Devidas M, Carroll AJ, Borowitz MJ, Bowman WP, Downing JR, Relling M, Yang J, Bhojwani D, Carroll WL, Camitta B, Reaman GH, Smith M, Hunger SP, Willman CL. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood. 2010 Dec 2;116(23):4874-84. doi: 10.1182/blood-2009-08-239681. Epub 2010 Aug 10.

  PMID: 20699438 BACKGROUND

• Yang JJ, Yang W, Cheng C, et al.: Genetically defined racial differences underlie risk of relapse in childhood acute lymphoblastic leukemia. [Abstract] Blood 112 (11): A-14, 2008.

  BACKGROUND

• Bowman WP, Larsen EL, Devidas M, Linda SB, Blach L, Carroll AJ, Carroll WL, Pullen DJ, Shuster J, Willman CL, Winick N, Camitta BM, Hunger SP, Borowitz MJ. Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: results of Children's Oncology Group trial P9906. Pediatr Blood Cancer. 2011 Oct;57(4):569-77. doi: 10.1002/pbc.22944. Epub 2011 Feb 25.

  PMID: 21360654 RESULT

• Zhang J, Mullighan CG, Harvey RC, Wu G, Chen X, Edmonson M, Buetow KH, Carroll WL, Chen IM, Devidas M, Gerhard DS, Loh ML, Reaman GH, Relling MV, Camitta BM, Bowman WP, Smith MA, Willman CL, Downing JR, Hunger SP. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Sep 15;118(11):3080-7. doi: 10.1182/blood-2011-03-341412. Epub 2011 Jun 16.

  PMID: 21680795 RESULT

• Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood. 2010 Jul 1;115(26):5312-21. doi: 10.1182/blood-2009-09-245944. Epub 2010 Feb 4.

  PMID: 20139093 RESULT

• Kang H, Chen IM, Wilson CS, Bedrick EJ, Harvey RC, Atlas SR, Devidas M, Mullighan CG, Wang X, Murphy M, Ar K, Wharton W, Borowitz MJ, Bowman WP, Bhojwani D, Carroll WL, Camitta BM, Reaman GH, Smith MA, Downing JR, Hunger SP, Willman CL. Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood. 2010 Feb 18;115(7):1394-405. doi: 10.1182/blood-2009-05-218560. Epub 2009 Oct 30.

  PMID: 19880498 RESULT

• Mullighan CG, Morin R, Zhang J, et al.: Next generation transcriptomic resequencing identifies novel genetic alterations in high-risk (HR) childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG) HR ALL TARGET Project. [Abstract] Blood 114 (22): A-704, 2009.

  RESULT

• Zhang J, Mullighan CG, Harvey RC, et al.: Mutations in the RAS signaling, B-cell development, TP53/RB1, and JAK signaling pathways are common in high risk B-precursor childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG) High-Risk (HR) ALL TARGET Project. [Abstract] Blood 114 (22): A-85, 2009.

  RESULT

• Harvey RC, Davidson GS, Wang X, et al.: Expression profiling identifies novel genetic subgroups with distinct clinical features and outcome in high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL). A Children's Oncology Group study. [Abstract] Blood 110 (11): A-1430, 2007.

  RESULT

• Kang H, Bedrick EJ, Chen IM, et al.: Molecular classifiers for prediction of minimal residual disease (MRD) and event free survival (EFS) improve risk assignment at diagnosis in pediatric high-risk B precursor acute lymphoblastic leukemia (ALL): a Childrens Oncology Group study. [Abstract] Blood 110 (11): A-1422, 2007.

  RESULT

• Borowitz MJ, Devidas M, Bowman WP, et al.: Prognostic significance of minimal residual disease (MRD) in children with high risk acute lymphoblastic leukemia(ALL): a Children's Oncology Group study. [Abstract] Blood 106 (11): A-85, 2005.

  RESULT

• Fernandez CA, Smith C, Yang W, Date M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Blood. 2014 Aug 21;124(8):1266-76. doi: 10.1182/blood-2014-03-563742. Epub 2014 Jun 26.

  PMID: 24970932 DERIVED

• Yang JJ, Cheng C, Devidas M, Cao X, Campana D, Yang W, Fan Y, Neale G, Cox N, Scheet P, Borowitz MJ, Winick NJ, Martin PL, Bowman WP, Camitta B, Reaman GH, Carroll WL, Willman CL, Hunger SP, Evans WE, Pui CH, Loh M, Relling MV. Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia. Blood. 2012 Nov 15;120(20):4197-204. doi: 10.1182/blood-2012-07-440107. Epub 2012 Sep 24.

  PMID: 23007406 DERIVED

MeSH Terms

Conditions

Leukemia

Interventions

Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Mercaptopurine; Methotrexate; Prednisone; Thioguanine; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Sulfhydryl Compounds; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• William P. Bowman, MD

  Cook Children's Medical Center - Fort Worth

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2000
• First Posted: January 27, 2003
• Study Start: March 1, 2000
• Primary Completion: September 1, 2005
• Last Updated: February 20, 2014

Record last verified: 2014-02

Locations

US (20)