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

Purpose

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium (LCV), 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 Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	High Risk B-Precursor Acute Lymphoblastic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia Steroids

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Childhood Acute Lymphoblastic Leukemia Lymphosarcoma

U.S. FDA Resources

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: 5 years ]
Event Free Probability.

Secondary Outcome Measures:

Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS) [ Time Frame: 5 Years ]
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS). [ Time Frame: 5 years ]
Bone marrow MRD status is defined as negative with < .01 detectable leukemia cells.
Correlation of Early Marrow Response Status With MRD Positive. [ Time Frame: Day 29 ]
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.
Correlation of Early Marrow Response Status With MRD Negative. [ Time Frame: Day 29 ]
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.
Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS) [ Time Frame: 5 years ]
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells.
Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS). [ Time Frame: 5 years ]
Bone marrow MRD status is defined as negative with < 0.1 detectable leukemia cells.


Enrollment:	3154
Study Start Date:	December 2003
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dexamethasone & Capizzi MTX patients<10 yrs Patients receive IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 & 2; IT MTX (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 & 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: Dexamethasone, High Dose (DH) MTX (non random) Patients non-randomly assigned to the DH regimen based on one (or more) of the following: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 & 2; IT MTX (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 & 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: Dexamethasone & Capizzi MTX patients =>10 yrs Patients receive IT 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 & 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 & 2; IT MTX (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 & 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: Dexamethasone during Induction, High Dose MTX (IM)<10 Patients randomly assigned to the DH regimen based on one (or more) of the following: (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 IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 & 2; IT MTX (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 & 29 (CNS3 also on days 15 & 22) and 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: 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, Capizzi (PC) MTX (<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 IT MTX in weeks 2 & 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, Capizzi MTX (>= 10 yrs) 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 IT MTX in weeks 2 & 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 and High Dose (PH) MTX (< 10 yrs) Patients randomly assigned to the PH regimen receive IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and IT MTX 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: 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 and High Dose MTX (>=10 yrs) Patients randomly assigned to the PH regimen receive IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and IT MTX in weeks 2 & 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning 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: Dexamethasone, High Dose MTX (IM) >=10 yrs 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 IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 & 2; IT MTX (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 & 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: 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, Capizzi MTX Down Syndrome (DS) (non random) 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 IT MTX in weeks 2 & 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: 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: Dexamethasone, Capizzi MTX DS (non random) Patients receive IT 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 & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 & 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 & 2; IT MTX (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 & High Dose MTX (non random) Patients non-randomly assigned to the PH regimen based on one (or more) of the following: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry or (3) extensive pre-treatment with steroids prior to entry. Patients receive IT 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, & 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15, & 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and IT MTX in weeks 2 & 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning 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

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Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:	1 Year to 30 Years (Child, Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00075725

Show 213 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Study Chair:	Eric C. Larsen, MD	Maine Children's Cancer Program at Barbara Bush Children's Hospital

More Information

Publications:

Winick NJ, Salzer WL, Devidas M, et al.: Dexamethasone (DEX) versus prednisone (PRED) during induction for children with high-risk acute lymphoblastic leukemia (HR-ALL): A report from the Children's Oncology Group Study AALL0232. [Abstract] J Clin Oncol 29 (Suppl 15): A-9504, 2011.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karol SE, Mattano LA Jr, Yang W, Maloney KW, Smith C, Liu C, Ramsey LB, Fernandez CA, Chang TY, Neale G, Cheng C, Mardis E, Fulton R, Scheet P, San Lucas FA, Larsen EC, Loh ML, Raetz EA, Hunger SP, Devidas M, Relling MV. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia. Blood. 2016 Feb 4;127(5):558-64. doi: 10.1182/blood-2015-10-673848. Epub 2015 Nov 20.

Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA Jr, Relling MV. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood. 2015 Oct 8;126(15):1770-6. doi: 10.1182/blood-2015-05-643601. Epub 2015 Aug 11.

Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, Nachman JB, Carroll AJ, Heerema NA, Gastier-Foster JM, Willman CL, Dai Y, Winick NJ, Hunger SP, Carroll WL, Larsen E. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232. Blood. 2015 Aug 20;126(8):964-71. doi: 10.1182/blood-2015-03-633685. Epub 2015 Jun 29.

Fernandez CA, Smith C, Yang W, Daté M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Blood. 2014 Aug 21;124(8):1266-76. doi: 10.1182/blood-2014-03-563742. Epub 2014 Jun 26.


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00075725 History of Changes
Other Study ID Numbers:	AALL0232 COG-AALL0232 ( Other Identifier: Children's Oncology Group ) NCI-2009-00301 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted:	January 9, 2004
First Posted:	January 13, 2004
Results First Submitted:	July 10, 2015
Results First Posted:	August 6, 2015
Last Update Posted:	March 21, 2017
Last Verified:	February 2017

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:


Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Dexamethasone acetate Dexamethasone Prednisone Liposomal doxorubicin Pegaspargase Cyclophosphamide	Doxorubicin Methotrexate Cytarabine Vincristine Daunorubicin Asparaginase 6-Mercaptopurine Thioguanine BB 1101 Levoleucovorin Leucovorin Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents