Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00075725
First received: January 9, 2004
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: prednisone
Drug: thioguanine
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Risk B-Precursor Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Comparison of the increase in cure rate of high risk ALL without causing more serious side effects between interventions [ Time Frame: During the first month of treatment ] [ Designated as safety issue: No ]
    Compared using a two-sided log rank test.


Secondary Outcome Measures:
  • Relative safety and efficacy [ Time Frame: Day 29 ] [ Designated as safety issue: Yes ]
    Relative safety and efficacy of each intervention. Adverse events (AE) are graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Compared using a two-sided log rank test.

  • Correlation of minimal residual disease (MRD) with event-free survival and overall survival [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.

  • Correlation of early marrow response status with MRD [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.

  • Additional high-risk patients for treatment with BFM [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    Identified using MRD


Enrollment: 3154
Study Start Date: December 2003
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dexamethasone and Capizzi Methotrexate patients < 10 years
Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6).
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: thioguanine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiation therapy periodically during study treatment
Active Comparator: Dexamethasone, High Dose Methotrexate (non randomly assigned)
Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6).
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: thioguanine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiation therapy periodically during study treatment
Active Comparator: Dexamethasone & Capizzi Methotrexate patients => 10 years old
Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6).
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: thioguanine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiation therapy periodically during study treatment
Active Comparator: Dexamethasone during Induction, High Dose Methotrexate (IM)
Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6).
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: thioguanine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiation therapy periodically during study treatment
Experimental: Prednisone, Capizzi methotrexate (<10 yrs old)
Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: doxorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: prednisone
Given IV or orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC #010023
Drug: thioguanine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiation therapy periodically during study treatment
Experimental: Prednisone, Capezzi methotrexate (>= 10 yrs old)
Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: doxorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: prednisone
Given IV or orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC #010023
Drug: thioguanine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiation therapy periodically during study treatment
Experimental: Predisone and High Dose Methotrexate (< 10 yrs old)
Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: prednisone
Given IV or orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC #010023
Experimental: Prenisone and High Dose Methotrexate (>=10 yrs old)
Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks
Drug: cyclophosphamide
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Cytoxan
  • NSC #2627
Drug: cytarabine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: daunorubicin hydrochloride
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • daunomycin
  • rubidomycin
  • Cerubidine
  • NSC #82151
Drug: dexamethasone
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: leucovorin calcium
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #00074
Drug: pegaspargase
Given IV, orally, intrathecally, intramuscularly, or subcutaneously
Other Names:
  • Peg-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC 624239
Drug: prednisone
Given IV or orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC #010023

  Hide Detailed Description

Detailed Description:

OBJECTIVES:

  • Compare the outcome of patients with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens.
  • Compare the relative safety and efficacy of dexamethasone vs prednisone during induction therapy in patients treated with these regimens.
  • Compare the relative safety and efficacy of high-dose methotrexate with leucovorin rescue vs escalating methotrexate without leucovorin rescue during interim maintenance I in patients treated with these regimens.
  • Correlate minimal residual disease (MRD) at day 29 with event-free survival and overall survival of patients treated with these regimens.
  • Correlate early marrow response status with day-29 MRD in patients treated with these regimens.
  • Identify additional high-risk patients for treatment with the fully augmented Berlin-Frankfurt-Munster regimen by using day-29 MRD.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to early response (slow early response [SER] vs rapid early response [RER]).

  • Induction therapy: Patients are randomized to 1 of 4 treatment arms.

    • Arm I: Patients receive intrathecal (IT) cytarabine on day 1; vincristine IV and daunorubicin IV on days 1, 8, 15, and 22; oral or IV dexamethasone twice daily on days 1-14; IT methotrexate (MTX) on days 8 and 29*; and pegaspargase intramuscularly (IM) once on day 4, 5, or 6.

NOTE: *Patients with CNS3 disease (WBC > 5/mL in cerebrospinal fluid and positive for blasts on cytospin) also receive IT MTX on days 15 and 22.

  • Arm II: Patients receive induction therapy as in arm I.
  • Arm III: Patients receive cytarabine, vincristine, daunorubicin, and pegaspargase as in arm I. Patients also receive oral or IV prednisone twice daily on days 1-28 and IT MTX on days 8 and 29.
  • Arm IV: Patients receive induction therapy as in arm III. Patients in all arms are evaluated at day 29 of induction therapy. Patients with M3 disease are removed from study. Patients with M1 disease and less than 1% minimal residual disease (MRD) proceed to consolidation therapy beginning on day 36. Patients with M2 disease OR with MI disease and at least 1% MRD receive extended induction therapy for 2 additional weeks. Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031.

    • Extended induction therapy: Patients continue to receive therapy on the arm to which they were originally randomized.
  • Arms I and II: Patients receive oral or IV dexamethasone twice daily on days 1-14; vincristine IV on days 1 and 8; daunorubicin IV on day 1; and pegaspargase IM on day 4, 5, or 6 and are then reevaluated.
  • Arms III and IV: Patients receive oral or IV prednisone twice daily on days 1-14, and vincristine, daunorubicin, and pegaspargase as in arms I and II and are then reevaluated.

Patients on all arms who have M1 disease and less than 1% MRD after extended induction proceed to consolidation therapy and continue as SER patients. All other patients are removed from study.

  • Consolidation therapy: All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine (MP) on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and IT MTX* on days 1, 8, 15, and 22. Patients with testicular disease also receive radiotherapy to the testes.

NOTE: *Patients with CNS3 disease receive MTX on days 1 and 8 only.

  • Interim maintenance therapy I: Patients continue to receive treatment on the arm to which they were originally randomized.

    • Arm I (escalating-dose MTX): Patients receive vincristine IV and escalating-dose MTX IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and IT MTX on days 1 and 21.
    • Arm II (high-dose MTX): Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; oral MP on days 1-56; and IT MTX on days 1 and 29. Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses, beginning 42 hours after start of each MTX infusion.
    • Arm III (escalating-dose MTX): Patients receive interim maintenance I therapy as in arm I.
    • Arm IV (high-dose MTX): Patients receive interim maintenance I therapy as in arm II.
  • Delayed intensification therapy I: All patients receive vincristine IV on days 1, 8, 15, 43, and 50; oral or IV dexamethasone twice daily on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over; doxorubicin IV on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6 AND day 43; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or SC on days 30-33 and 37-40; oral thioguanine on days 29-42; and IT MTX on days 1, 29, and 36.

After delayed intensification I, SER patients proceed to interim maintenance II and delayed intensification II. RER patients proceed directly to maintenance.

  • Interim maintenance therapy II: All patients receive vincristine IV and MTX IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and IT MTX on days 1 and 21. Patients then proceed to delayed intensification II.
  • Delayed intensification therapy II: All patients receive therapy as in delayed intensification I, arm I. CNS3 patients also receive radiotherapy for 3-10 days, beginning on day 29. All other SER patients, patients with MLL rearrangements, and some patients pretreated with steroids (> 48 hours within the week prior to diagnosis) receive prophylactic cranial radiotherapy (CRT) for 8 days, beginning on day 29. Patients then proceed to maintenance therapy.
  • Maintenance therapy: All patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral MP on days 1-84; IT MTX on day 1*; and oral MTX on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.

NOTE: *RER (who did not undergo CRT) patients also receive IT MTX on day 29 for maintenance courses 1-4.

In all arms, maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients. Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy.

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 annually thereafter.

PROJECTED ACCRUAL: A total of 2,964 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed B-precursor acute lymphoblastic leukemia

    • WBC > 50,000/mm^3 for patients age 1 to 9
    • Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease
  • Must be eligible for and enrolled on classification study COG-AALL03B1

PATIENT CHARACTERISTICS:

Age

  • 1 to under 31

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Not specified

Renal

  • Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No more than 72 hours since prior intrathecal cytarabine
  • No other prior cytotoxic chemotherapy

Endocrine therapy

  • Prior steroids allowed

Radiotherapy

  • Not specified

Surgery

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075725

  Show 213 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Eric C. Larsen, MD Maine Children's Cancer Program at Barbara Bush Children's Hospital
  More Information

Additional Information:
Publications:
Raetz EA, Devidas M, Carroll AJ, et al.: Cytogenetic and early-response characteristics of adolescents and young adults with acute lymphoblastic leukemia (ALL): A Children's Oncology Group (COG) study. [Abstract] J Clin Oncol 28 (Suppl 15): A-9509, 2010.
Mattano LA Jr, Nachman JB, Devidas M, et al.: Increased incidence of osteonecrosis (ON) with a dexamethasone (DEX) induction for high risk acute lymphoblastic leukemia (HR-ALL): a report from the Children's Oncology Group (COG). [Abstract] Blood 112 (11): A-898, 2008.
Bleyer A: Older adolescents and young adults with acute lymphoblastic leukemia (ALL) in the United States: from the lowest to highest death rate and number of deaths--more rationale for the CALBG-SWOG-ECOG C10403 trial based on COG AALL0232. [Abstract] J Clin Oncol 26 (Suppl 15): A-18034, 2008.
Harvey RC, Chen IM, Ar K, et al.: Identification of novel cluster groups in high-risk pediatric B-precursor acute lymphoblastic leukemia (HR-ALL) by gene expression profiling: correlation with clinical and outcome variables a Children's Oncology Group (COG) study. [Abstract] Blood 112 (11): A-2256, 2008.
Maloney KW, Larsen E, Mattano LA, et al.: Increased infection-related mortality for children with Down syndrome (DS) in contemporary Childrens Oncology Group (COG) acute lymphoblastic leukemia (ALL) clinical trials. [Abstract] Blood 108 (11): A-1865, 2006.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00075725     History of Changes
Other Study ID Numbers: AALL0232, COG-AALL0232, CDR0000349182
Study First Received: January 9, 2004
Last Updated: August 6, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
B-cell adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
6-Mercaptopurine
Liposomal doxorubicin
Pegaspargase
Dexamethasone
Doxorubicin
Prednisone
Vincristine
Asparaginase
Daunorubicin
Thioguanine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Levoleucovorin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014