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Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: cyclophosphamide (Drug); cytarabine (Drug); daunorubicin hydrochloride (Drug); dexamethasone (Drug); leucovorin calcium (Drug); mercaptopurine (Drug); methotrexate (Drug); pegaspargase (Drug); thioguanine (Drug); vincristine sulfate (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Paul L. Martin, MD, Study Chair, Affiliation: Duke Cancer Institute


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 may kill more cancer cells. It is not yet known which regimen of combination chemotherapy is more effective for childhood acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is comparing different regimens of combination chemotherapy to see how well they work in treating children with acute lymphoblastic leukemia.

Clinical Details

Official title: ALINC #17 Treatment for Patients With Low Risk Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Phase III Study

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Event-free survival

Occurrence of anticipated failures

Grade 3 or greater CNS toxicity rates assessed using NCI CTC version 2.0

Secondary outcome:

Measures of laboratory factors (other than MRD)

Homocysteine levels

Detailed description: OBJECTIVES:

- Compare the efficacy and toxicity of short methotrexate infusion vs longer infusion in

patients with low-risk acute lymphoblastic leukemia.

- Compare the efficacy of these regimens of methotrexate, with or without multidrug

intensification, in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to genetics (stratum 1: trisomy 4/10 but not TEL/AML1 vs stratum 2: TEL/AML1 with or without trisomy 4/10). All patients receive induction therapy (weeks 1-4) on another protocol (POG-9900). Stratum 1

- Consolidation therapy begins on week 5. Patients are randomized to arm I or II.

- Arm I: Patients receive methotrexate (MTX) IV over 24 hours on day 1 and oral

leucovorin calcium (CF) every 6 hours for 3 doses beginning 42 hours after initiation of MTX infusion during weeks 7, 10, 13, 16, and 19.

- Arm II: Patients receive MTX IV over 4 hours on day 1 and oral CF as in arm I

during weeks 7, 10, 13, 16, and 19.

- Patients in arms I and II also receive MTX intrathecally (IT) on weeks 7, 10, 13, 16,

19, and 22; oral mercaptopurine (6-MP) daily on weeks 5-24; oral dexamethasone (DM) twice daily on days 1-7 of weeks 8 and 17; and vincristine (VCR) IV on day 1 of weeks 8, 9, 17, and 18. Stratum 2

- Consolidation therapy begins on week 5 and delayed intensification therapy begins on

week 16. Patients are randomized to delayed intensification or no delayed intensification. Patients randomized to no delayed intensification are then randomized to consolidation therapy on arm I or II. Patients randomized to delayed intensification are then randomized to arm III or IV. Patients with trisomy 4/10 are not randomized to arms III and IV.

- Arm III: Patients receive MTX IV and CF as in arm I on weeks 7, 10, 13, 24, 27,

and 30.

- Arm IV: Patients receive MTX IV and CF as in arm II on weeks 7, 10, 13, 24, 27,

and 30.

- Patients in arms III and IV also receive oral 6-MP daily on weeks 5-13 and then

beginning on week 24 and continuing until the end of consolidation; MTX IT on weeks 7, 10, 13, 16, 20, 21, and 30; oral DM twice daily on days 1-7 of weeks 8, 16-18, and 28; VCR IV on day 1 of weeks 8, 9, 16-18, 28, and 29; pegaspargase intramuscularly on week 16; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV on day 1 of week 20; cytarabine IV or subcutaneously on days 2-5 of weeks 20 and 21; and oral thioguanine daily on days 1-14 of weeks 20 and 21. All patients then receive continuation therapy beginning on week 25 for arms I and II and week 33 for arms III and IV and continuing until week 130 for all arms. Continuation

- Arms I and II: Patients receive oral 6-MP daily on weeks 25-130; oral DM twice a day on

days 1-7 and VCR IV on days 1 and 8 during weeks 25, 41, 57, 73, 89, and 105; oral MTX weekly on weeks 25-130 (except during weeks of IT MTX); and MTX IT on weeks 25, 37, 49, 61, 73, 85, 97, and 109.

- Arms III and IV: Patients receive oral 6-MP daily on weeks 33-130; oral DM twice a day

on days 1-7 and VCR IV on days 1 and 8 during weeks 41, 57, 73, 89, and 105; oral MTX weekly on weeks 33-130 (except during weeks of IT MTX); and MTX IT on weeks 37, 49, 61, 73, 85, 97, and 109. Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total 902 patients will be accrued for this study within 3. 22 years.


Minimum age: 1 Year. Maximum age: 9 Years. Gender(s): Both.



- Diagnosis of B-cell precursor acute lymphoblastic leukemia

- Registered on POG-9900 Classification Study

- Registered within 7 days of documenting complete response (CR) after induction

therapy on day 29 or, if 2 more weeks of induction are required, within 7 days of CR determination

- Classified as low-risk:

- WBC less than 50,000/mm^3

- Age 1 to 9

- No adverse translocations [E2A-PBX1, t(1;19) or BCR/ABL, t(9;22); and MLL


- No CNS 3 disease (CSF WBC at least 5/mm^3 with blasts present)

- No testicular disease

- At least one of the following present:

- TEL/AML1, t(12;21)

- Simultaneous trisomy of chromosomes 4 and 10


- 1 to 9

Performance status:

- Not specified

Life expectancy:

- Not specified


- See Disease Characteristics


- Not specified


- Not specified


- Not pregnant or nursing

- Fertile patients must use effective contraception


- Not specified


- Not specified

Endocrine therapy

- Not specified


- Not specified


- Not specified

Locations and Contacts

University Medical Center Groningen, Groningen 9700 RB, Netherlands

San Jorge Children's Hospital, Santurce 00912, Puerto Rico

Swiss Pediatric Oncology Group Bern, Bern CH 3010, Switzerland

Swiss Pediatric Oncology Group Geneva, Geneva CH 1211, Switzerland

Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, Alabama 35233, United States

University of South Alabama Cancer Research Institute, Mobile, Alabama 36604, United States

Alberta Children's Hospital, Calgary, Alberta T2T 5C7, Canada

Cross Cancer Institute at University of Alberta, Edmonton, Alberta T6G 1Z2, Canada

Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson, Arizona 85724, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Rebecca and John Moores UCSD Cancer Center, La Jolla, California 92093-0658, United States

Stanford Cancer Center at Stanford University Medical Center, Palo Alto, California 94304-1812, United States

Sutter Cancer Center, Sacramento, California 95816, United States

University of California Davis Cancer Center, Sacramento, California 95817, United States

Children's Hospital and Health Center - San Diego, San Diego, California 92123-4282, United States

Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego, San Diego, California 92120, United States

Kaiser Permanente Medical Center - Santa Clara Kiely Campus, Santa Clara, California 95051-5386, United States

Yale Comprehensive Cancer Center, New Haven, Connecticut 06520-8064, United States

Broward General Medical Center, Fort Lauderdale, Florida 33316, United States

Children's Hospital of Southwest Florida, Fort Myers, Florida 33908, United States

University of Florida Shands Cancer Center, Gainesville, Florida 32610-0296, United States

Joe DiMaggio Children's Hospital at Memorial, Hollywood, Florida 33021, United States

Nemours Children's Clinic, Jacksonville, Florida 32207, United States

Baptist-South Miami Regional Cancer Program, Miami, Florida 33176-2197, United States

Miami Children's Hospital, Miami, Florida 33155, United States

University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 30101, United States

Florida Hospital Cancer Institute, Orlando, Florida 32804, United States

Nemours Children's Clinic-Orlando, Orlando, Florida 32806, United States

Sacred Heart Children's Hospital, Pensacola, Florida 32504, United States

All Children's Hospital, St. Petersburg, Florida 33701, United States

St. Joseph's Children's Hospital of Tampa, Tampa, Florida 33677-4227, United States

Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus, Atlanta, Georgia 30342, United States

MBCCOP-Medical College of Georgia Cancer Center, Augusta, Georgia 30912-4000, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States

Tripler Army Medical Center, Honolulu, Hawaii 96859-5000, United States

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Advocate Hope Children's Hospital, Oak Lawn, Illinois 60453, United States

Saint Jude Midwest Affiliate, Peoria, Illinois 61637, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

CCOP - Wichita, Wichita, Kansas 67214-3882, United States

Via Christi Cancer Center at Via Christi Regional Medical Center, Wichita, Kansas 67214, United States

Wesley Medical Center, Wichita, Kansas 67214, United States

Children's Hospital of New Orleans, New Orleans, Louisiana 70118, United States

MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana 70112, United States

Ochsner Cancer Institute at Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States

Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans, Louisiana 70112, United States

Pediatric Specialty Clinic at Eastern Maine Medical Center, Bangor, Maine 04401, United States

Maine Children's Cancer Program, Scarborough, Maine 04074-9308, United States

Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore, Maryland 21201-1595, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-7223, United States

Walter Reed Army Medical Center, Silver Spring, Maryland 20910, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States

Floating Hospital for Children, Boston, Massachusetts 02111, United States

Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114-2696, United States

UMASS Memorial Cancer Center - University Campus, Worcester, Massachusetts 01655, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center, Detroit, Michigan 48236, United States

Hurley Medical Center, Flint, Michigan 48503, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Keesler Medical Center - Keesler Air Force Base, Keesler AFB, Mississippi 39534-2511, United States

University of Missouri - Columbia, Columbia, Missouri 65203, United States

Cardinal Glennon Children's Hospital, Saint Louis, Missouri 63104, United States

St. Louis Children's Hospital, Saint Louis, Missouri 63110, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

University of New Mexico Cancer Research and Treatment Center, Albuquerque, New Mexico 87131, United States

Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States

Schneider Children's Hospital, New Hyde Park, New York 11040, United States

Beth Israel Medical Center - Singer Division, New York, New York 10128, United States

Mount Sinai Medical Center, New York, New York 10029, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States

Long Island Cancer Center at Stony Brook University Hospital, Stony Brook, New York 11794-8174, United States

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States

Mission Hospitals - Memorial Campus, Asheville, North Carolina 28801, United States

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Presbyterian Cancer Center at Presbyterian Hospital, Charlotte, North Carolina 28233, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital, Greenville, North Carolina 27858-4354, United States

Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1081, United States

Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States

Natalie Warren Bryant Cancer Center at St. Francis Hospital, Tulsa, Oklahoma 74136, United States

McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8S 4J9, Canada

Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

CCOP - Columbia River Oncology Program, Portland, Oregon 97225, United States

Legacy Emanuel Hospital and Health Center & Children's Hospital, Portland, Oregon 97227, United States

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3G 1A4, Canada

Centre de Recherche du Centre Hospitalier de l'Universite Laval, Sainte Foy, Quebec GIV 4G2, Canada

Royal Children's Hospital, Brisbane, Queensland 4029, Australia

Rhode Island Hospital, Providence, Rhode Island 02903, United States

Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States

Children's Hospital of Greenville Hospital System, Greenville, South Carolina 29605, United States

East Tennessee State University Cancer Center at Johnson City Medical Center, Johnson City, Tennessee 37614-0622, United States

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States

Driscoll Children's Hospital, Corpus Christi, Texas 78466, United States

Medical City Dallas Hospital, Dallas, Texas 75230, United States

Simmons Cancer Center at University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063, United States

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States

University of Texas Medical Branch, Galveston, Texas 77555-0209, United States

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital, Houston, Texas 77030-2399, United States

San Antonio Military Pediatric Cancer and Blood Disorders Center, Lackland Air Force Base, Texas 78236, United States

MBCCOP - South Texas Pediatrics, San Antonio, Texas 78229-3900, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States

CCOP - Scott and White Hospital, Temple, Texas 76508, United States

Center for Cancer Prevention and Care at Scott and White Clinic, Temple, Texas 76508, United States

Vermont Cancer Center at University of Vermont, Burlington, Vermont 05401-3498, United States

Royal Children's Hospital, Parkville, Victoria 3052, Australia

University of Virginia Cancer Center, Charlottesville, Virginia 22908, United States

INOVA Fairfax Hospital, Falls Church, Virginia 22042-3300, United States

Naval Medical Center - Portsmouth, Portsmouth, Virginia 23708-5100, United States

Massey Cancer Center at Virginia Commonwealth University, Richmond, Virginia 23298-0121, United States

Carilion Medical Center for Children at Roanoke Community Hospital, Roanoke, Virginia 24029, United States

Madigan Army Medical Center, Tacoma, Washington 98431-0001, United States

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division, Charleston, West Virginia 25302, United States

Mary Babb Randolph Cancer Center at West Virginia University Hospitals, Morgantown, West Virginia 26506-9300, United States

St. Vincent Hospital, Green Bay, Wisconsin 54307-9070, United States

CCOP - Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, United States

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Related publications:

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.

Xu H, Cheng C, Devidas M, Pei D, Fan Y, Yang W, Neale G, Scheet P, Burchard EG, Torgerson DG, Eng C, Dean M, Antillon F, Winick NJ, Martin PL, Willman CL, Camitta BM, Reaman GH, Carroll WL, Loh M, Evans WE, Pui CH, Hunger SP, Relling MV, Yang JJ. ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol. 2012 Mar 1;30(7):751-7. doi: 10.1200/JCO.2011.38.0345. Epub 2012 Jan 30.

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.

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.

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.

Hinds PS, Hockenberry MJ, Gattuso JS, Srivastava DK, Tong X, Jones H, West N, McCarthy KS, Sadeh A, Ash M, Fernandez C, Pui CH. Dexamethasone alters sleep and fatigue in pediatric patients with acute lymphoblastic leukemia. Cancer. 2007 Nov 15;110(10):2321-30.

Winick N, Martin PL, Devidas M, et al.: Delayed intensification (DI) enhances event-free survival (EFS) of children with B-precursor acute lymphoblastic leukemia (ALL) who received intensification therapy with six courses of intravenous methotrexate (MTX): POG 9904/9905: a Children's Oncology Group study (COG). [Abstract] Blood 110 (11): A-583, 2007.

Starting date: April 2000
Last updated: June 7, 2013

Page last updated: August 23, 2015

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