Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

April 4, 2023 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

838

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Children's Hospital at Westmead
    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Royal Children's Hospital
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • Alberta Children's Hospital
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute at University of Alberta
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4J9
        • McMaster Children's Hospital at Hamilton Health Sciences
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
      • Montreal, Quebec, Canada, H3G 1A4
        • Montreal Children's Hospital at McGill University Health Center
      • Sainte Foy, Quebec, Canada, GIV 4G2
        • Centre de Recherche du Centre Hospitalier de l'Universite Laval
  • Netherlands
      • Groningen, Netherlands, 9700 RB
        • University Medical Center Groningen
  • Puerto Rico
      • Santurce, Puerto Rico, 00912
        • San Jorge Children's Hospital
  • Switzerland
      • Bern, Switzerland, CH 3010
        • Swiss Pediatric Oncology Group Bern
      • Geneva, Switzerland, CH 1211
        • Swiss Pediatric Oncology Group Geneva
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Comprehensive Cancer Center at University of Alabama at Birmingham
      • Mobile, Alabama, United States, 36604
        • University of South Alabama Cancer Research Institute
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Arizona Cancer Center at University of Arizona Health Sciences Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • California
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Palo Alto, California, United States, 94304-1812
        • Stanford Cancer Center at Stanford University Medical Center
      • Sacramento, California, United States, 95816
        • Sutter Cancer center
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center
      • San Diego, California, United States, 92120
        • Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
      • San Diego, California, United States, 92123-4282
        • Children's Hospital and Health Center - San Diego
      • Santa Clara, California, United States, 95051-5386
        • Kaiser Permanente Medical Center - Santa Clara Kiely Campus
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8064
        • Yale Comprehensive Cancer Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward General Medical Center
      • Fort Myers, Florida, United States, 33908
        • Children's Hospital of Southwest Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of Florida Shands Cancer Center
      • Hollywood, Florida, United States, 33021
        • Joe DiMaggio Children's Hospital at Memorial
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Miami, Florida, United States, 33155
        • Miami Children's Hospital
      • Miami, Florida, United States, 33176-2197
        • Baptist-South Miami Regional Cancer Program
      • Miami, Florida, United States, 30101
        • University of Miami Sylvester Comprehensive Cancer Center
      • Orlando, Florida, United States, 32804
        • Florida Hospital Cancer Institute
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic-Orlando
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Children's Hospital
      • Saint Petersburg, Florida, United States, 33701
        • All Children's Hospital
      • Tampa, Florida, United States, 33677-4227
        • St. Joseph's Children's Hospital of Tampa
      • West Palm Beach, Florida, United States, 33407
        • Kaplan Cancer Center at St. Mary's Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
      • Augusta, Georgia, United States, 30912-4000
        • MBCCOP-Medical College of Georgia Cancer Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96859-5000
        • Tripler Army Medical Center
      • Honolulu, Hawaii, United States, 96813
        • Cancer Research Center of Hawaii
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Hope Children's Hospital
      • Peoria, Illinois, United States, 61637
        • Saint Jude Midwest Affiliate
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
      • Wichita, Kansas, United States, 67214-3882
        • CCOP - Wichita
      • Wichita, Kansas, United States, 67214
        • Wesley Medical Center
      • Wichita, Kansas, United States, 67214
        • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital of New Orleans
      • New Orleans, Louisiana, United States, 70112
        • MBCCOP - LSU Health Sciences Center
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Cancer Institute at Ochsner Clinic Foundation
      • New Orleans, Louisiana, United States, 70112
        • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Maine
      • Bangor, Maine, United States, 04401
        • Pediatric Specialty Clinic at Eastern Maine Medical Center
      • Scarborough, Maine, United States, 04074-9308
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21201-1595
        • Greenebaum Cancer Center at University of Maryland Medical Center
      • Baltimore, Maryland, United States, 21231-7223
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Silver Spring, Maryland, United States, 20910
        • Walter Reed Army Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Floating Hospital for Children
      • Boston, Massachusetts, United States, 02114-2696
        • Massachusetts General Hospital Cancer Center
      • Worcester, Massachusetts, United States, 01655
        • UMASS Memorial Cancer Center - University Campus
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
      • Detroit, Michigan, United States, 48236
        • Van Elslander Cancer Center at St. John Hospital and Medical Center
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Medical Center
      • Keesler Air Force Base, Mississippi, United States, 39534-2511
        • Keesler Medical Center - Keesler Air Force Base
    • Missouri
      • Columbia, Missouri, United States, 65203
        • University of Missouri - Columbia
      • Saint Louis, Missouri, United States, 63110
        • St. Louis Children's Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Cancer Research and Treatment Center
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • New Hyde Park, New York, United States, 11040
        • Schneider Children's Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10128
        • Beth Israel Medical Center - Singer Division
      • Rochester, New York, United States, 14642
        • James P. Wilmot Cancer Center at University of Rochester Medical Center
      • Stony Brook, New York, United States, 11794-8174
        • Long Island Cancer Center at Stony Brook University Hospital
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Mission Hospitals - Memorial Campus
      • Charlotte, North Carolina, United States, 28232-2861
        • Blumenthal Cancer Center at Carolinas Medical Center
      • Charlotte, North Carolina, United States, 28233
        • Presbyterian Cancer Center at Presbyterian Hospital
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Greenville, North Carolina, United States, 27858-4354
        • Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital
      • Winston-Salem, North Carolina, United States, 27157-1081
        • Comprehensive Cancer Center at Wake Forest University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Medical center
      • Tulsa, Oklahoma, United States, 74136
        • Natalie Warren Bryant Cancer Center at St. Francis Hospital
    • Oregon
      • Portland, Oregon, United States, 97225
        • CCOP - Columbia River Oncology Program
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center & Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134-1095
        • St. Christopher's Hospital for Children
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Hollings Cancer Center at Medical University of South Carolina
      • Greenville, South Carolina, United States, 29605
        • Children's Hospital of Greenville Hospital System
    • Tennessee
      • Johnson City, Tennessee, United States, 37614-0622
        • East Tennessee State University Cancer Center at Johnson City Medical Center
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Corpus Christi, Texas, United States, 78466
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Dallas, Texas, United States, 75390-9063
        • Simmons Cancer Center at University of Texas Southwestern Medical Center at Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Galveston, Texas, United States, 77555-0209
        • University of Texas Medical Branch
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
      • Lackland Air Force Base, Texas, United States, 78236
        • San Antonio Military Pediatric Cancer and Blood Disorders Center
      • San Antonio, Texas, United States, 78207
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229-3900
        • MBCCOP - South Texas Pediatrics
      • Temple, Texas, United States, 76508
        • CCOP - Scott and White Hospital
      • Temple, Texas, United States, 76508
        • Center for Cancer Prevention and Care at Scott and White Clinic
    • Vermont
      • Burlington, Vermont, United States, 05401-3498
        • Vermont Cancer Center at University of Vermont
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Falls Church, Virginia, United States, 22042-3300
        • Inova Fairfax Hospital
      • Portsmouth, Virginia, United States, 23708-5100
        • Naval Medical Center - Portsmouth
      • Richmond, Virginia, United States, 23298-0121
        • Massey Cancer Center at Virginia Commonwealth University
      • Roanoke, Virginia, United States, 24029
        • Carilion Medical Center for Children at Roanoke Community Hospital
    • Washington
      • Tacoma, Washington, United States, 98431-0001
        • Madigan Army Medical Center
    • West Virginia
      • Charleston, West Virginia, United States, 25302
        • West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
      • Morgantown, West Virginia, United States, 26506-9300
        • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54307-9070
        • St. Vincent Hospital
      • Marshfield, Wisconsin, United States, 54449
        • CCOP - Marshfield Clinic Research Foundation
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 9 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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 rearrangements]
    • 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

PATIENT CHARACTERISTICS:

Age:

  • 1 to 9

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

  • Not specified

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I: (combination chemotherapy)
CONSOLIDATION: Pts receive Methotrexate(MTX) IV over 24 hrs on day 1 and oral leucovorin calcium (CF) every 6 hrs for 3 doses at 42 hours after initiation of MTX infusion during weeks 7, 10, 13, 16, and 19. Pts also receive MTX IT on wks 7, 10, 13, 16, 19, and 22; oral mercaptopurine(6-MP) daily wks 5-24; oral dexamethasone (DM) 2x on days 1-7 of wks 8 and 17; and vincristine sulfate (VCR) IV on day 1 of wks 8, 9, 17, and 18. CONTINUATION: Pts receive oral 6-MP daily on wks 25-130; oral DM twice a day on days 1-7 and vincristine sulfate (VCR) IV on days 1 and 8 during wks 25, 41, 57, 73, 89, and 105; oral MTX on wks 25-130 (except during wks of IT MTX); and MTX IT on wks 25, 37, 49, 61, 73, 85, 97, and 109.
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • LCR
  • NSC #67574
Drug: dexamethasone
Dexamethasone is a synthetic fluorinated glucocorticoid devoid of mineralocorticoid effects.
Other Names:
  • Decadron
  • NSC#034521
Drug: leucovorin calcium
Synthetic d,l-5 CHO tetrahydrofolate, which is used to bypass the inhibition of dihydrofolate reductase by Methotrexate (MTX)
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC#003590
Drug: mercaptopurine
An analogue of the nucleic acid constituent adenine and the physiological purine base hypoxanthine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #00075
Drug: methotrexate
A folate analogue which inhibits the enzyme dihydrofolate reductase, haltin g DNA, RNA, and protein synthesis
Other Names:
  • amethopterin
  • MTX
  • NSC#00740
  • IND#4291
Experimental: Arm II (combination chemotherapy)
CONSOLIDATION: Pts receive methotrexate (MTX) IV over 4 hrs on day 1 and oral leucovorin calcium (CF) during wks 7, 10, 13, 16, and 19. Pts also receive MTX IT on wks 7, 10, 13, 16, 19, and 22; oral mercaptopurine (6-MP) daily on wks 5-24; oral dexamethasone (DM) 2x on days 1-7 of wks 8 and 17; and vincristine sulfate (VCR) IV on day 1 of wks 8, 9, 17, and 18. CONTINUATION: Pts receive oral 6-MP daily on wks 25-130; oral DM 2x on days 1-7 and vincristine sulfate (VCR) IV on days 1 and 8 during wks 25, 41, 57, 73, 89, and 105; oral MTX weekly on wks 25-130 (except during wks of IT MTX); and MTX IT on wks 25, 37, 49, 61, 73, 85, 97, and 109.
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • LCR
  • NSC #67574
Drug: dexamethasone
Dexamethasone is a synthetic fluorinated glucocorticoid devoid of mineralocorticoid effects.
Other Names:
  • Decadron
  • NSC#034521
Drug: leucovorin calcium
Synthetic d,l-5 CHO tetrahydrofolate, which is used to bypass the inhibition of dihydrofolate reductase by Methotrexate (MTX)
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC#003590
Drug: mercaptopurine
An analogue of the nucleic acid constituent adenine and the physiological purine base hypoxanthine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #00075
Drug: methotrexate
A folate analogue which inhibits the enzyme dihydrofolate reductase, haltin g DNA, RNA, and protein synthesis
Other Names:
  • amethopterin
  • MTX
  • NSC#00740
  • IND#4291
Experimental: Arm III (combination chemotherapy)
CONSOLIDATION: Pts receive methotrexate (MTX) IV and leucovorin calcium (CF) as in arm I on wks 7, 10, 13, 24, 27, and 30. Pts also receive oral mercaptopurine (6-MP) daily on wks 5-13 and then on wk 24 and continuing until the end of consolidation; MTX IT on wks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone (DM) twice daily on days 1-7 of wks 8, 16-18, and 28; vincristine sulfate (VCR) IV on day 1 of wks 8, 9, 16-18, 28, and 29; pegaspargase intramuscularly on wk 16; daunorubicin hydrochloride IV on day 1 of wks 16-18; cyclophosphamide IV on day 1 of wk 20; cytarabine IV or subcutaneously on days 2-5 of wks 20 and 21; and oral thioguanine daily on days 1-14 of wks 20 and 21. CONTINUATION: Pts receive oral 6-MP daily on wks 33-130; oral dexamethasone (DM) twice a day on days 1-7 and VCR IV on days 1 and 8 during wks 41, 57, 73, 89, and 105; oral MTX weekly on wks 33-130 (except during wks of IT MTX); and MTX IT on wks 37, 49, 61, 73, 85, 97, and 109.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • LCR
  • NSC #67574
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidine
  • NSC #82151
  • Daunomycin
  • rubidomycin
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • Lanvis
  • Tabloid
  • WR-1141
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • NSC # 752
Drug: dexamethasone
Dexamethasone is a synthetic fluorinated glucocorticoid devoid of mineralocorticoid effects.
Other Names:
  • Decadron
  • NSC#034521
Drug: leucovorin calcium
Synthetic d,l-5 CHO tetrahydrofolate, which is used to bypass the inhibition of dihydrofolate reductase by Methotrexate (MTX)
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC#003590
Drug: mercaptopurine
An analogue of the nucleic acid constituent adenine and the physiological purine base hypoxanthine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #00075
Drug: methotrexate
A folate analogue which inhibits the enzyme dihydrofolate reductase, haltin g DNA, RNA, and protein synthesis
Other Names:
  • amethopterin
  • MTX
  • NSC#00740
  • IND#4291
Drug: cytarabine
Deoxycytidine analogue which is metabolized to ARA-CTP, a substance which inhibits DNA polymerase.
Other Names:
  • Ara-C
  • Cytosar
  • cytosine arabinoside
  • NSC #063878
Drug: pegaspargase
E-Coli asparaginase deaminates asparagine, thus, is lethal for cells which cannot synthesize asparagine.
Other Names:
  • Elspar
  • PEG
  • asparaginase
  • NSC#109229
  • E Coli
  • Erwinia
Experimental: .Arm IV (combination chemotherapy)
CONSOLIDATION: Pts receive methotrexate (MTX) and leucovorin calcium (CF) on wks 7, 10, 13, 24, 27, and 30. Pts receive mercaptopurine(6-MP) daily weeks 5-13 then beginning wk 24 and continuing until end of consolidation; MTX on wks 7, 10, 13, 16, 20, 21, and 30; dexamethasone (DM) 2x daily on days 1-7 of wks 8, 16-18, and 28; vincristine sulfate (VCR) day 1 of wks 8, 9, 16-18, 28, and 29; pegaspargase on wk 16; daunorubicin hydrochloride on day 1 of wks 16-18; cyclophosphamide on day 1 of wk 20; cytarabine on days 2-5 of wks 20 and 21; thioguanine daily on days 1-14 of wks 20 and 21. CONTINUATION: Pts receive mercaptopurine(6-MP) daily on weeks 33-130; oral dexamethasone (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 IV MTX); and IV MTX on weeks 37, 49, 61, 73, 85, 97, and 109.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • LCR
  • NSC #67574
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidine
  • NSC #82151
  • Daunomycin
  • rubidomycin
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • Lanvis
  • Tabloid
  • WR-1141
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • NSC # 752
Drug: dexamethasone
Dexamethasone is a synthetic fluorinated glucocorticoid devoid of mineralocorticoid effects.
Other Names:
  • Decadron
  • NSC#034521
Drug: leucovorin calcium
Synthetic d,l-5 CHO tetrahydrofolate, which is used to bypass the inhibition of dihydrofolate reductase by Methotrexate (MTX)
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC#003590
Drug: mercaptopurine
An analogue of the nucleic acid constituent adenine and the physiological purine base hypoxanthine
Other Names:
  • 6-MP
  • Purinethol
  • NSC #00075
Drug: methotrexate
A folate analogue which inhibits the enzyme dihydrofolate reductase, haltin g DNA, RNA, and protein synthesis
Other Names:
  • amethopterin
  • MTX
  • NSC#00740
  • IND#4291
Drug: cytarabine
Deoxycytidine analogue which is metabolized to ARA-CTP, a substance which inhibits DNA polymerase.
Other Names:
  • Ara-C
  • Cytosar
  • cytosine arabinoside
  • NSC #063878
Drug: pegaspargase
E-Coli asparaginase deaminates asparagine, thus, is lethal for cells which cannot synthesize asparagine.
Other Names:
  • Elspar
  • PEG
  • asparaginase
  • NSC#109229
  • E Coli
  • Erwinia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: 4 years
The test statistic will compare Kaplan-Meier curves with sample size derived from a modification of the Makuch-Simon method for historical controls
4 years
Occurrence of anticipated failures
Time Frame: Up to 7 years
An O'Brien-Fleming analysis will be conducted, with significance declared if the observed logrank Z-statistic exceeds the z/sqrt(IF), where IF=fraction of anticipated failures that have occurred and z=critical value of the final analysis.
Up to 7 years
Grade 3 or greater CNS toxicity rates assessed using NCI CTC version 2.0
Time Frame: Up to 7 years
Up to 7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measures of laboratory factors (other than MRD)
Time Frame: Up to 7 years
Cox multiple regression will be utilized.
Up to 7 years
Homocysteine levels
Time Frame: Up to 7 years
Will be correlated to acute neurotoxicity by Cox regression.
Up to 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Paul L. Martin, MD, Duke Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2000

Primary Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

May 2, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

April 6, 2023

Last Update Submitted That Met QC Criteria

April 4, 2023

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9904
  • COG-P9904 (Other Identifier: Children's Oncology Group)
  • POG-9904 (Other Identifier: Pediatric Oncology Group)
  • CDR0000067657 (Other Identifier: Clinical Trials.gov)
  • NCI-2012-02321 (Other Identifier: NCI)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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