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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

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ClinicalTrials.gov Identifier: NCT00075725
Recruitment Status : Completed
First Posted : January 13, 2004
Results First Posted : August 6, 2015
Last Update Posted : September 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia
Interventions 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
Enrollment 3154
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Hide Arm/Group Description 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). Patients non-randomly assigned to the DH (High Dose) 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). 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). 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). Patients in regimen PC (Prednisone, Capizzi) 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. 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. Patients randomly assigned to the PH (Prednisone, High Dose MTX) 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. 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. 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). 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. 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). 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 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 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.
Period Title: Overall Study
Started 246 106 296 246 232 710 246 696 302 34 12 28
Completed 172 57 175 168 166 397 171 401 185 16 3 10
Not Completed 74 49 121 78 66 313 75 295 117 18 9 18
Reason Not Completed
Adverse Event             6             6             20             8             4             38             3             51             15             4             2             2
Death             3             5             10             2             3             25             4             22             14             4             3             0
Lost to Follow-up             1             1             4             1             0             13             2             4             1             0             0             0
Physician Decision             2             6             5             8             4             19             3             17             5             0             1             0
Pregnancy             0             0             0             0             0             1             0             1             0             0             0             0
Protocol Violation             1             1             0             3             3             2             1             2             3             0             0             1
Withdrawal by Subject             12             3             6             10             6             27             7             31             10             2             0             0
Disease Progression, all other reasons             17             5             33             6             21             59             20             46             21             4             0             5
Patient off treatment             0             0             1             2             1             0             0             2             1             0             0             0
Ineligible or wrong diagnosis             8             3             3             10             3             17             6             9             10             1             2             4
Pt/Guardian refused RT therapy             1             0             1             2             1             0             0             0             0             0             0             0
Pt non compliant with therapy             2             1             1             0             2             14             2             5             3             0             0             0
Pt age out of range for treatment             0             1             0             0             0             1             0             1             0             0             0             0
Insurance issues             0             1             0             1             1             1             0             1             0             0             0             0
MRD positive after extended ind             0             1             1             0             1             2             0             1             0             0             0             0
Pt has very high risk ALL characteristic             15             11             26             18             11             75             23             74             29             1             0             3
Inevaluable             1             1             4             2             2             9             1             11             2             0             1             0
Other             4             2             1             1             1             4             2             9             2             1             0             3
Pt trying to find a BM donor             0             1             0             0             0             0             0             0             0             0             0             0
Clinic chart lost unable to recreate             0             0             1             0             0             0             0             0             0             0             0             0
Unsuccessful institutional transfer             0             0             2             0             0             0             0             0             0             1             0             0
specimen(s) not submitted             0             0             2             0             0             0             0             0             0             0             0             0
Pt went to transplant             0             0             0             1             0             1             0             0             0             0             0             0
Pt received additional steroids             0             0             0             1             0             0             0             0             0             0             0             0
Pt relocated             0             0             0             2             0             1             1             2             1             0             0             0
Institution Terminated             0             0             0             0             1             0             0             3             0             0             0             0
Study Closure             1             0             0             0             1             3             0             1             0             0             0             0
Other complications             0             0             0             0             0             1             0             0             0             0             0             0
Pt care terminated due to pt behavior             0             0             0             0             0             0             0             1             0             0             0             0
Pt incarcerated             0             0             0             0             0             0             0             1             0             0             0             0
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome Prednisone and High Dose Methotrexate (Non Randomly Assigned) Total
Hide Arm/Group Description 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). 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). 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). 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). 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. 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. 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. 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. 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). 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. 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). Patients non-randomly assigned to the PH 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. 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 Total of all reporting groups
Overall Number of Baseline Participants 246 106 296 246 232 710 246 696 302 34 12 28 3154
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 106 participants 296 participants 246 participants 232 participants 710 participants 246 participants 696 participants 302 participants 34 participants 12 participants 28 participants 3154 participants
<=18 years
246
 100.0%
96
  90.6%
275
  92.9%
246
 100.0%
232
 100.0%
641
  90.3%
246
 100.0%
610
  87.6%
266
  88.1%
30
  88.2%
10
  83.3%
26
  92.9%
2924
  92.7%
Between 18 and 65 years
0
   0.0%
10
   9.4%
21
   7.1%
0
   0.0%
0
   0.0%
69
   9.7%
0
   0.0%
86
  12.4%
36
  11.9%
4
  11.8%
2
  16.7%
2
   7.1%
230
   7.3%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 246 participants 106 participants 296 participants 246 participants 232 participants 710 participants 246 participants 696 participants 302 participants 34 participants 12 participants 28 participants 3154 participants
4.0  (2.3) 9.3  (6.0) 14.1  (2.8) 4.1  (2.2) 4.2  (2.2) 14.7  (3.3) 4.2  (2.2) 14.5  (3.2) 14.6  (2.9) 10.5  (5.7) 12.3  (6.6) 14.4  (2.9) 10.8  (5.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 106 participants 296 participants 246 participants 232 participants 710 participants 246 participants 696 participants 302 participants 34 participants 12 participants 28 participants 3154 participants
Female
129
  52.4%
31
  29.2%
135
  45.6%
117
  47.6%
106
  45.7%
321
  45.2%
108
  43.9%
288
  41.4%
128
  42.4%
18
  52.9%
7
  58.3%
11
  39.3%
1399
  44.4%
Male
117
  47.6%
75
  70.8%
161
  54.4%
129
  52.4%
126
  54.3%
389
  54.8%
138
  56.1%
408
  58.6%
174
  57.6%
16
  47.1%
5
  41.7%
17
  60.7%
1755
  55.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 106 participants 296 participants 246 participants 232 participants 710 participants 246 participants 696 participants 302 participants 34 participants 12 participants 28 participants 3154 participants
Hispanic or Latino
54
  22.0%
22
  20.8%
62
  20.9%
55
  22.4%
62
  26.7%
167
  23.5%
61
  24.8%
168
  24.1%
69
  22.8%
6
  17.6%
0
   0.0%
7
  25.0%
733
  23.2%
Not Hispanic or Latino
179
  72.8%
81
  76.4%
217
  73.3%
182
  74.0%
165
  71.1%
516
  72.7%
179
  72.8%
504
  72.4%
219
  72.5%
27
  79.4%
10
  83.3%
20
  71.4%
2299
  72.9%
Unknown or Not Reported
13
   5.3%
3
   2.8%
17
   5.7%
9
   3.7%
5
   2.2%
27
   3.8%
6
   2.4%
24
   3.4%
14
   4.6%
1
   2.9%
2
  16.7%
1
   3.6%
122
   3.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 106 participants 296 participants 246 participants 232 participants 710 participants 246 participants 696 participants 302 participants 34 participants 12 participants 28 participants 3154 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
0
   0.0%
4
   0.6%
1
   0.4%
7
   1.0%
2
   0.7%
1
   2.9%
2
  16.7%
0
   0.0%
18
   0.6%
Asian
8
   3.3%
6
   5.7%
11
   3.7%
9
   3.7%
7
   3.0%
21
   3.0%
8
   3.3%
27
   3.9%
18
   6.0%
2
   5.9%
0
   0.0%
0
   0.0%
117
   3.7%
Native Hawaiian or Other Pacific Islander
2
   0.8%
1
   0.9%
1
   0.3%
2
   0.8%
1
   0.4%
5
   0.7%
5
   2.0%
6
   0.9%
2
   0.7%
0
   0.0%
0
   0.0%
0
   0.0%
25
   0.8%
Black or African American
12
   4.9%
14
  13.2%
24
   8.1%
12
   4.9%
15
   6.5%
55
   7.7%
14
   5.7%
51
   7.3%
19
   6.3%
2
   5.9%
0
   0.0%
1
   3.6%
219
   6.9%
White
196
  79.7%
76
  71.7%
235
  79.4%
187
  76.0%
175
  75.4%
534
  75.2%
187
  76.0%
519
  74.6%
227
  75.2%
26
  76.5%
9
  75.0%
24
  85.7%
2395
  75.9%
More than one race
3
   1.2%
3
   2.8%
1
   0.3%
8
   3.3%
5
   2.2%
8
   1.1%
5
   2.0%
4
   0.6%
3
   1.0%
0
   0.0%
0
   0.0%
0
   0.0%
40
   1.3%
Unknown or Not Reported
25
  10.2%
6
   5.7%
24
   8.1%
27
  11.0%
29
  12.5%
83
  11.7%
26
  10.6%
82
  11.8%
31
  10.3%
3
   8.8%
1
   8.3%
3
  10.7%
340
  10.8%
1.Primary Outcome
Title Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
Hide Description Event Free Probability.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Group “Prednisone and High Dose MTX (non-random)” who either had EFS events occur before 5 years or did not have minimum 5 years of follow-up.
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Predisone and High Dose Methotrexate < 10 Yrs Old Prenisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prenisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random)
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
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.
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).
Overall Number of Participants Analyzed 218 90 261 206 214 598 213 601 262 30 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
83.2
(76.6 to 89.9)
81.6
(71.2 to 91.9)
69.1
(63.1 to 75.2)
91.2
(85.7 to 96.7)
82.1
(75.3 to 89.0)
73.5
(67.4 to 79.7)
80.8
(73.6 to 88.0)
75.8
(70.0 to 81.6)
77.0
(71.5 to 82.6)
61.8
(43.1 to 80.5)
44.4
(12.0 to 76.9)
2.Secondary Outcome
Title Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS)
Hide Description Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
Time Frame 5 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Groups "Prednisone Capizzi MTX (Down's Syndrome)", "Dexamethasone, Capizzi MTX (non-random)" & "Prednisone and High Dose MTX (non-random) are not included in this OM as no patients survived the 5 year window for analysis. Cohort of MRD Positive patients who either had EFS/OS events occur before 5 years or did not have minimum 5 years of follow-up.
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capizzi Methotrexate >= 10 Years Predisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
Overall Number of Participants Analyzed 28 13 53 15 17 116 20 112 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
79.2
(59.5 to 98.8)
69.9
(32.4 to 100)
65.6
(50.2 to 81.0)
86.2
(49.9 to 100)
93.8
(70.8 to 100)
63.1
(49.4 to 76.8)
84.2
(66.53 to 100)
73.6
(59.8 to 87.4)
74.6
(60.9 to 88.3)
3.Secondary Outcome
Title Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS).
Hide Description Bone marrow MRD status is defined as negative with < .01 detectable leukemia cells.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients on Arm/Group "Prednisone and High Dose Methotrexate (non randomly assigned)" are not included in the OM as there were no survivors for the 5 year duration. Cohort of MRD Negative patients some of whom have had EFS/OS events after 5 years or have minimum 5 years of follow-up.
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capizzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capizzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random)
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
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.
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).
Overall Number of Participants Analyzed 185 73 198 189 195 472 191 480 209 25 4
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.4
(91.3 to 99.4)
92.9
(85.4 to 100)
87.4
(82.5 to 92.4)
98.1
(95.4 to 100)
93.3
(88.6 to 98.0)
90.2
(85.5 to 94.9)
94.5
(90.0 to 98.9)
90.5
(86.1 to 95.0)
91.6
(87.5 to 95.8)
78.3
(61.0 to 95.7)
25.0
(-17.4 to 67.4)
4.Secondary Outcome
Title Correlation of Early Marrow Response Status With MRD Positive.
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
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.
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).
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 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 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.
Overall Number of Participants Analyzed 28 13 53 15 17 116 20 112 44 3 3 5
Measure Type: Number
Unit of Measure: participants
26 12 43 14 16 95 17 98 39 3 3 3
5.Secondary Outcome
Title Correlation of Early Marrow Response Status With MRD Negative.
Hide Description 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.
Time Frame Day 29
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
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.
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).
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 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 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.
Overall Number of Participants Analyzed 185 73 198 189 195 472 191 480 209 25 4 18
Measure Type: Number
Unit of Measure: participants
182 72 198 188 195 471 190 479 208 25 3 18
6.Secondary Outcome
Title Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS)
Hide Description Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells.
Time Frame 5 years
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Hide Analysis Population Description
Groups "Prednisone Capizzi MTX (Down's Syndrome)", "Dexamethasone, Capizzi MTX (non-random)" & "Prednisone and High Dose MTX (non-random) are not included in this OM as no patients survived the 5 year window for analysis. Cohort of MRD Positive patients who either had EFS/OS events occur before 5 years or did not have minimum 5 years of follow-up.
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capizzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
Overall Number of Participants Analyzed 28 13 53 15 17 116 20 112 44
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
66.5
(43.7 to 89.2)
43.3
(6.4 to 80.2)
35.4
(21.4 to 49.3)
80
(30.4 to 100)
34.7
(-4.2 to 73.5)
39
(25.7 to 52.4)
55
(29.4 to 80.6)
47.8
(32.3 to 63.3)
49.4
(34.0 to 64.8)
7.Secondary Outcome
Title Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS).
Hide Description Bone marrow MRD status is defined as negative with < 0.1 detectable leukemia cells.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Group “Prednisone and High Dose MTX (non-random)” who either had EFS/OS events occur before 5 years or did not have minimum 5 years of follow-up.
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random)
Hide Arm/Group Description:
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).
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).
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).
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).
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.
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.
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.
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.
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).
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.
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).
Overall Number of Participants Analyzed 185 73 198 189 195 472 191 480 209 25 4
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
86.4
(79.8 to 93.1)
93.6
(86.3 to 100)
80.5
(74.5 to 86.4)
93.1
(88.1 to 98.2)
86.5
(80.2 to 92.8)
83.4
(77.5 to 89.4)
84.2
(77.2 to 91.3)
83.9
(78.3 to 89.5)
85.3
(80. to 90.5)
74.4
(55.9 to 92.8)
25
(-17.4 to 67.4)
Time Frame [Not Specified]
Adverse Event Reporting Description SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
 
Arm/Group Title Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Hide Arm/Group Description 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). 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). 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). 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). 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. 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. 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. 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. 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). 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. 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). 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 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 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.
All-Cause Mortality
Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dexamethasone and Capizzi Methotrexate Patients < 10 Years Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old Dexamethasone, High Dose Methotrexate (IM) < 10 Years Prednisone, Capizzi Methotrexate <10 Years Prednisone, Capezzi Methotrexate >= 10 Years Prednisone and High Dose Methotrexate < 10 Yrs Old Prednisone and High Dose Methotrexate >=10 Years Dexamethasone, High Dose Methotrexate (IM) >= 10 Years Prednisone, Capezzi Methotrexate (Down's Syndrome) Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) Prednisone and High Dose Methotrexate (Non Randomly Assigned)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/218 (7.34%)      17/90 (18.89%)      42/261 (16.09%)      25/206 (12.14%)      20/214 (9.35%)      64/598 (10.70%)      16/213 (7.51%)      67/601 (11.15%)      27/262 (10.31%)      3/30 (10.00%)      3/9 (33.33%)      1/23 (4.35%)    
Blood and lymphatic system disorders                         
Anemia  1/218 (0.46%)  1 0/90 (0.00%)  0 2/261 (0.77%)  2 4/206 (1.94%)  5 1/214 (0.47%)  1 4/598 (0.67%)  4 0/213 (0.00%)  0 2/601 (0.33%)  2 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Blood and lymphatic system disorders - Other, specify  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  2 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Bone marrow hypocellular  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Disseminated intravascular coagulation  0/218 (0.00%)  0 2/90 (2.22%)  2 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 3/601 (0.50%)  3 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Febrile neutropenia  4/218 (1.83%)  7 0/90 (0.00%)  0 2/261 (0.77%)  2 2/206 (0.97%)  3 2/214 (0.93%)  2 4/598 (0.67%)  4 0/213 (0.00%)  0 1/601 (0.17%)  1 3/262 (1.15%)  3 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hemolysis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Cardiac disorders                         
Cardiac arrest  0/218 (0.00%)  0 1/90 (1.11%)  1 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Cardiac disorders - Other, specify  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Left ventricular systolic dysfunction  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0
Myocardial infarction  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Sinus tachycardia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Ventricular tachycardia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Endocrine disorders                         
Adrenal insufficiency  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Eye disorders                         
Eye disorders - Other, specify  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Gastrointestinal disorders                         
Abdominal distension  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Abdominal pain  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Ascites  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 2/206 (0.97%)  2 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Colitis  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Colonic perforation  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Constipation  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Diarrhea  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 1/23 (4.35%)  1
Enterocolitis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Esophagitis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Ileal hemorrhage  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Ileal perforation  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 1/213 (0.47%)  1 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Jejunal perforation  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Lower gastrointestinal hemorrhage  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Mucositis oral  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 2/598 (0.33%)  2 0/213 (0.00%)  0 3/601 (0.50%)  3 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Nausea  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Oral pain  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Pancreatitis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 1/598 (0.17%)  1 1/213 (0.47%)  1 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Rectal mucositis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Small intestinal perforation  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 1/213 (0.47%)  1 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Typhlitis  0/218 (0.00%)  0 0/90 (0.00%)  0 2/261 (0.77%)  2 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 1/213 (0.47%)  1 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Vomiting  0/218 (0.00%)  0 1/90 (1.11%)  1 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 1/598 (0.17%)  1 0/213 (0.00%)  0 3/601 (0.50%)  3 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
General disorders                         
Fever  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
General disorders and administration site conditions - Other, specify  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Multi-organ failure  1/218 (0.46%)  1 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 1/598 (0.17%)  1 1/213 (0.47%)  1 2/601 (0.33%)  2 2/262 (0.76%)  2 1/30 (3.33%)  1 0/9 (0.00%)  0 0/23 (0.00%)  0
Pain  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 2/206 (0.97%)  2 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Sudden death NOS  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hepatobiliary disorders                         
Hepatic failure  0/218 (0.00%)  0 0/90 (0.00%)  0 4/261 (1.53%)  4 0/206 (0.00%)  0 0/214 (0.00%)  0 5/598 (0.84%)  5 0/213 (0.00%)  0 1/601 (0.17%)  1 2/262 (0.76%)  2 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hepatic pain  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hepatobiliary disorders - Other, specify  0/218 (0.00%)  0 0/90 (0.00%)  0 2/261 (0.77%)  2 1/206 (0.49%)  2 1/214 (0.47%)  1 1/598 (0.17%)  1 1/213 (0.47%)  1 0/601 (0.00%)  0 2/262 (0.76%)  3 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Portal hypertension  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 2/206 (0.97%)  2 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0
Immune system disorders                         
Allergic reaction  1/218 (0.46%)  1 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Anaphylaxis  1/218 (0.46%)  1 1/90 (1.11%)  1 0/261 (0.00%)  0 1/206 (0.49%)  1 1/214 (0.47%)  1 5/598 (0.84%)  5 0/213 (0.00%)  0 3/601 (0.50%)  3 1/262 (0.38%)  1 1/30 (3.33%)  1 0/9 (0.00%)  0 0/23 (0.00%)  0
Infections and infestations                         
Appendicitis perforated  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Bronchial infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Enterocolitis infectious  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 2/598 (0.33%)  2 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hepatitis viral  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Infections and infestations - Other, specify  3/218 (1.38%)  7 6/90 (6.67%)  6 11/261 (4.21%)  13 2/206 (0.97%)  2 2/214 (0.93%)  2 13/598 (2.17%)  17 4/213 (1.88%)  4 12/601 (2.00%)  17 5/262 (1.91%)  8 1/30 (3.33%)  1 2/9 (22.22%)  2 0/23 (0.00%)  0
Lip infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Lung infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 2/598 (0.33%)  2 1/213 (0.47%)  1 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Otitis media  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Pharyngitis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Sepsis  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 2/598 (0.33%)  2 0/213 (0.00%)  0 2/601 (0.33%)  2 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Skin infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  2 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Soft tissue infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Upper respiratory infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Urinary tract infection  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Injury, poisoning and procedural complications                         
Vascular access complication  1/218 (0.46%)  1 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Investigations                         
Activated partial thromboplastin time prolonged  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 2/601 (0.33%)  2 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Alanine aminotransferase increased  1/218 (0.46%)  3 0/90 (0.00%)  0 2/261 (0.77%)  2 4/206 (1.94%)  4 1/214 (0.47%)  1 6/598 (1.00%)  6 3/213 (1.41%)  3 3/601 (0.50%)  3 1/262 (0.38%)  1 1/30 (3.33%)  1 0/9 (0.00%)  0 0/23 (0.00%)  0
Aspartate aminotransferase increased  1/218 (0.46%)  1 1/90 (1.11%)  1 2/261 (0.77%)  2 4/206 (1.94%)  5 0/214 (0.00%)  0 4/598 (0.67%)  4 1/213 (0.47%)  1 4/601 (0.67%)  4 2/262 (0.76%)  2 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Blood bilirubin increased  0/218 (0.00%)  0 0/90 (0.00%)  0 3/261 (1.15%)  4 1/206 (0.49%)  1 0/214 (0.00%)  0 6/598 (1.00%)  7 0/213 (0.00%)  0 3/601 (0.50%)  3 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Cholesterol high  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Creatinine increased  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
GGT increased  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 2/598 (0.33%)  2 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
INR increased  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Investigations - Other, specify  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 2/206 (0.97%)  2 0/214 (0.00%)  0 1/598 (0.17%)  1 1/213 (0.47%)  2 2/601 (0.33%)  2 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Lipase increased  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 1/213 (0.47%)  1 2/601 (0.33%)  2 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Lymphocyte count decreased  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 2/206 (0.97%)  2 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Neutrophil count decreased  2/218 (0.92%)  2 1/90 (1.11%)  1 5/261 (1.92%)  5 6/206 (2.91%)  6 3/214 (1.40%)  3 5/598 (0.84%)  6 4/213 (1.88%)  4 2/601 (0.33%)  2 4/262 (1.53%)  4 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Platelet count decreased  0/218 (0.00%)  0 0/90 (0.00%)  0 4/261 (1.53%)  4 1/206 (0.49%)  2 1/214 (0.47%)  1 4/598 (0.67%)  4 0/213 (0.00%)  0 2/601 (0.33%)  2 3/262 (1.15%)  3 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Serum amylase increased  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Weight gain  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Weight loss  0/218 (0.00%)  0 1/90 (1.11%)  1 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
White blood cell decreased  1/218 (0.46%)  1 1/90 (1.11%)  1 3/261 (1.15%)  3 2/206 (0.97%)  2 0/214 (0.00%)  0 3/598 (0.50%)  3 0/213 (0.00%)  0 2/601 (0.33%)  2 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Metabolism and nutrition disorders                         
Acidosis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 2/601 (0.33%)  3 3/262 (1.15%)  3 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Alkalosis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 1/206 (0.49%)  1 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Anorexia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 2/598 (0.33%)  2 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Dehydration  0/218 (0.00%)  0 1/90 (1.11%)  1 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 2/598 (0.33%)  2 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Glucose intolerance  0/218 (0.00%)  0 1/90 (1.11%)  1 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypercalcemia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hyperglycemia  0/218 (0.00%)  0 0/90 (0.00%)  0 2/261 (0.77%)  2 0/206 (0.00%)  0 0/214 (0.00%)  0 5/598 (0.84%)  5 0/213 (0.00%)  0 3/601 (0.50%)  3 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hyperkalemia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypermagnesemia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypernatremia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypertriglyceridemia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hyperuricemia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypoalbuminemia  0/218 (0.00%)  0 2/90 (2.22%)  2 1/261 (0.38%)  1 1/206 (0.49%)  1 0/214 (0.00%)  0 1/598 (0.17%)  1 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypocalcemia  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 2/598 (0.33%)  2 0/213 (0.00%)  0 1/601 (0.17%)  1 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypoglycemia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hypokalemia  0/218 (0.00%)  0 1/90 (1.11%)  1 1/261 (0.38%)  1 0/206 (0.00%)  0 1/214 (0.47%)  1 2/598 (0.33%)  2 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Hyponatremia  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 3/598 (0.50%)  3 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Iron overload  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  4 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Tumor lysis syndrome  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Musculoskeletal and connective tissue disorders                         
Abdominal soft tissue necrosis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Avascular necrosis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 1/598 (0.17%)  2 0/213 (0.00%)  0 1/601 (0.17%)  1 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Back pain  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Generalized muscle weakness  0/218 (0.00%)  0 0/90 (0.00%)  0 1/261 (0.38%)  1 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Muscle weakness lower limb  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Osteoporosis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 1/601 (0.17%)  1 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Pain in extremity  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Pelvic soft tissue necrosis  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 1/262 (0.38%)  1 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Soft tissue necrosis lower limb  0/218 (0.00%)  0 1/90 (1.11%)  1 0/261 (0.00%)  0 0/206 (0.00%)  0 0/214 (0.00%)  0 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                         
Leukemia secondary to oncology chemotherapy  0/218 (0.00%)  0 0/90 (0.00%)  0 0/261 (0.00%)  0 0/206 (0.00%)  0 1/214 (0.47%)  1 0/598 (0.00%)  0 0/213 (0.00%)  0 0/601 (0.00%)  0 0/262 (0.00%)  0 0/30 (0.00%)  0 0/9 (0.00%)  0