Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

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

ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A 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 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.

Study Overview

Detailed Description

OBJECTIVES:

  • Determine if multidrug delayed-intensification therapy improves outcome in children with newly diagnosed standard-risk acute lymphocytic leukemia.
  • Compare the efficacy and toxicity of methotrexate administered over 4 hours vs methotrexate administered over 24 hours in this patient population.
  • Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.

OUTLINE: This is a randomized, multicenter study.

  • Induction (weeks 1-4): Patients receive induction therapy on POG 9900.
  • Consolidation (weeks 5-32): Patients are randomized to one of four treatment arms. Patients with t(1;19) are randomized to either arm III or arm IV.

    • Arm I (weeks 5-24): Patients receive IT methotrexate (MTX) on day 1 followed by MTX IV over 20 minutes followed by MTX continuously over 23.6 hours on weeks 7, 10, 13, 16,19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium every 6 hours for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on week 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of weeks 8 and 17; and vincristine IV on day 1 of weeks 8, 9, 17, and 18.
    • Arm II (weeks 5-24): Patients receive MTX IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine, and IT MTX as in arm I.
    • Arm III (weeks 5-32): Patients receive MTX 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 week 16; and oral mercaptopurine daily on weeks 5-13, and from week 24 until the completion of consolidation therapy. Patients also receive IT MTX as in arm I on weeks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone twice daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine IV on day 1 of weeks 8, 9, 16, 17, 18, 28, and 29; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of weeks 20 and 21; and oral thioguanine daily on weeks 20-21.
    • Arm IV (weeks 5-32): Patients receive MTX IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT MTX, dexamethasone, vincristine, daunorubicin, cyclophosphamide, cytarabine, and thioguanine as in arm III.
  • Intensive continuation (weeks 25-80): At weeks 25-72 for arms I and II, and at weeks 33-80 for arms III and IV, patients receive oral MTX every 6 hours for 4 doses on weeks 1, 3, 5, 7, 9, and 11; oral mercaptopurine daily; oral leucovorin calcium every 12 hours for 2 doses beginning 48 hours after the start of MTX; IT MTX and vincristine IV on day 1 of week 12; and oral dexamethasone twice daily on days 1-7, beginning with the administration of vincristine. Treatment repeats every 12 weeks for 4 courses.
  • Additional continuation (weeks 73-130): At weeks 73-130 for arms I and II, and at weeks 81-130 for arms III and IV, patients receive oral MTX weekly; oral mercaptopurine daily; vincristine IV on day 1 every 12 weeks; oral dexamethasone as during intensive continuation therapy; and IT MTX on day 1 every 12 weeks, beginning with the last week of the first course (in place of oral MTX).

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then every 6-12 months for 1 year.

PROJECTED ACCRUAL: A total of 1,014 patients will be accrued for this study within 3.22 years.

Study Type

Interventional

Enrollment (Actual)

1076

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

    • 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
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • Alberta Children's Hospital
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • 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
      • Groningen, Netherlands, 9700 RB
        • University Medical Center Groningen
      • Santurce, Puerto Rico, 00912
        • San Jorge Children's Hospital
      • Bern, Switzerland, CH 3010
        • Swiss Pediatric Oncology Group Bern
      • Geneva, Switzerland, CH 1211
        • Swiss Pediatric Oncology Group Geneva
    • 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
    • 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
      • 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, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Baltimore, Maryland, United States, 21201-1595
        • Greenebaum Cancer Center at University of Maryland Medical Center
      • 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
        • Cancer Center at 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, 11042
        • 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
        • 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 - 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
        • Cancer Center at the University of Virginia
      • Falls Church, Virginia, United States, 22042-3300
        • Inova Fairfax Hospital
      • Portsmouth, Virginia, United States, 23708-5100
        • Naval Medical Center - Portsmouth
      • Richmond, Virginia, United States, 23298-0212
        • 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 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of newly diagnosed B-precursor acute lymphocytic leukemia
  • Standard risk (not low, high, or very high risk)
  • Prior registration and treatment on POG 9900 Classification Study

PATIENT CHARACTERISTICS:

Age:

  • 1 to 21 at diagnosis

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

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
Patients 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.
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Names:
  • DEX
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
Other Names:
  • 6-MP

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.

Other Names:
  • MTX
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Names:
  • VCR
Experimental: Arm II
Patients 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.
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Names:
  • DEX
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
Other Names:
  • 6-MP

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.

Other Names:
  • MTX
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Names:
  • VCR
Experimental: Arm III
Patients 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.
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Names:
  • DEX
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
Other Names:
  • 6-MP

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.

Other Names:
  • MTX
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Names:
  • VCR
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
Other Names:
  • daunomycin
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
Other Names:
  • PEG
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.
Other Names:
  • 6-TG
Experimental: Arm IV
Patients 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.
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Names:
  • DEX
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
Other Names:
  • 6-MP

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.

Other Names:
  • MTX
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Names:
  • VCR
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
Other Names:
  • daunomycin
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
Other Names:
  • PEG
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.
Other Names:
  • 6-TG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in outcome in children receiving multidrug delayed-intensification therapy
Time Frame: Up to 4 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival, minimal residual disease, and early response
Time Frame: 5 years
The test statistic will compare Kaplan-Meier curves. Cox multiple regression will be utilized.
5 years
Occurrence of anticipated failures
Time Frame: Up to 5 years
An O'Brien-Fleming analysis will be conducted.
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
Time Frame: Up to 5 years
Up to 5 years

Collaborators and Investigators

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

Investigators

  • Study Chair: Naomi J. Winick, MD, Simmons Cancer Center

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

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, 2005

Study 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

May 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • 9905
  • COG-P9905 (Other Identifier: Children's Oncology Group)
  • POG-9905 (Other Identifier: Pediatric Oncology Group)
  • CDR0000067704 (Other Identifier: Clinical Trials.gov)
  • NCI-2012-02325 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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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