Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study
5 other identifiers
interventional
1,076
6 countries
123
Brief 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 may kill more cancer cells. It is not yet known which regimen of chemotherapy is more effective for acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is comparing four regimens of combination chemotherapy to see how well they work in treating children with newly diagnosed acute lymphoblastic leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 leukemia
Started Apr 2000
Typical duration for phase_3 leukemia
123 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2000
CompletedFirst Submitted
Initial submission to the registry
May 2, 2000
CompletedFirst Posted
Study publicly available on registry
January 27, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2005
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2007
CompletedApril 6, 2023
May 1, 2016
5.3 years
May 2, 2000
April 4, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Improvement in outcome in children receiving multidrug delayed-intensification therapy
The overall plan is to accrue for 3.1 years or until all accrual goals have been met, whichever occurs first. Since power is determined by event-rates, lower or higher than expected event rates could lead to an amendment to alter the accrual goal. This consideration will be made independent of arm-specific outcome, in order to eliminate bias
Up to 4 years
Secondary Outcomes (3)
Event-free survival, minimal residual disease, and early response
5 years
Occurrence of anticipated failures
Up to 5 years
Total grade 3+ central nervous system (CNS) toxicity rates based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to 5 years
Study Arms (4)
Arm I
EXPERIMENTALPatients receive IT methotrexate on day 1 followed by methotrexate IV over 20 minutes followed by methotrexate continuously over 23.6 hrs on wks 7, 10, 13, 16,19, and 22. At 42 hrs after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium every 6 hrs for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on wk 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of wks 8 and 17; and vincristine sulfate IV on day 1 of wks 8, 9, 17, and 18.
Arm II
EXPERIMENTALPatients receive methotrexate IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine sulfate, and IT methotrexate as in arm I.
Arm III
EXPERIMENTALPatients receive methotrexate IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of wk 16; oral mercaptopurine daily on wks 5-13, and from wk 24 until the completion of consolidation therapy. Patients also receive IT methotrexate as in arm I on wks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone 2x daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine sulfate IV on day 1 of wks 8, 9, 16, 17, 18, 28, and 29; daunorubicin hydrochloride IV on day 1 of wks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of wks 20 and 21; and oral thioguanine daily on wks 20-21.
Arm IV
EXPERIMENTALPatients receive methotrexate IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT methotrexate, dexamethasone, vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, cytarabine, and thioguanine as in arm III.
Interventions
30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC \> 500/μL and platelets \> 75,000/uL
IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.
2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; \> or = 1 day after the IT MTX
60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC \> or = 500/ul and platelets \> or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression.
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Eligibility Criteria
Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (123)
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
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
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
San Diego, California, 92120, United States
Children's Hospital and Health Center, San Diego
San Diego, California, 92123-4282, United States
Kaiser Permanente Medical Center - Santa Clara
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
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 30101, United States
Miami Children's Hospital
Miami, Florida, 33155, United States
Baptist-South Miami Regional Cancer Program
Miami, Florida, 33176-2197, 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
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
Rush University Medical Center
Chicago, Illinois, 60612, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60614, 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
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, 70112, United States
Tulane Cancer Center at Tulane University Hospital and Clinic
New Orleans, Louisiana, 70112, United States
Children's Hospital of New Orleans
New Orleans, Louisiana, 70118, United States
Ochsner Cancer Institute at Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, 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, 21231-2410, United States
Walter Reed Army Medical Center
Silver Spring, Maryland, 20910, United States
Floating Hospital for Children
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114-2696, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115, 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 Air Force Base, Mississippi, 39534-2511, United States
University of Missouri - Columbia
Columbia, Missouri, 65203, United States
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104, United States
St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Cancer Center at 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
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001, United States
Schneider Children's Hospital
New Hyde Park, New York, 11042, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Beth Israel Medical Center - Singer Division
New York, New York, 10128, 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, 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
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
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 - 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
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78207, United States
MBCCOP - South Texas Pediatrics
San Antonio, Texas, 78229-3900, 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
Cancer Center at the University of Virginia
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, 23298-0212, 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
Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Royal Children's Hospital
Brisbane, Queensland, 4029, Australia
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Alberta Children's Hospital
Calgary, Alberta, T2T 5C7, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
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
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, H3G 1A4, Canada
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5, Canada
Centre de Recherche du Centre Hospitalier de l'Universite Laval
Sainte-Foy, Quebec, GIV 4G2, Canada
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
Related Publications (11)
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: 22368272BACKGROUNDRabin 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: 22102553BACKGROUNDXu 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.
PMID: 22291082BACKGROUNDBorowitz 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.
BACKGROUNDBorowitz 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: 18388178BACKGROUNDDavies 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: 18182569BACKGROUNDHinds 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. doi: 10.1002/cncr.23039.
PMID: 17926333BACKGROUNDWinick 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.
BACKGROUNDChen I, Harvey R, Mullighan CG, et al.: Relationship of CRLF2 expression and outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): A report from the Children's Oncology Group. [Abstract] J Clin Oncol 29 (Suppl 15): A-9505, 2011.
RESULTRamsey LB, Panetta JC, Smith C, Yang W, Fan Y, Winick NJ, Martin PL, Cheng C, Devidas M, Pui CH, Evans WE, Hunger SP, Loh M, Relling MV. Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood. 2013 Feb 7;121(6):898-904. doi: 10.1182/blood-2012-08-452839. Epub 2012 Dec 11.
PMID: 23233662DERIVEDYang 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: 23007406DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Naomi J. Winick, MD
Simmons Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2000
First Posted
January 27, 2003
Study Start
April 1, 2000
Primary Completion
July 1, 2005
Study Completion
July 1, 2007
Last Updated
April 6, 2023
Record last verified: 2016-05