High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 3,154
- 试验地点
- 234
- 主要终点
- Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
研究概览
简要总结
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia (ALL). Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.
详细描述
OBJECTIVES:
I. Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens.
II. Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction.
III. Determine the relative safety and efficacy of high-dose methotrexate (5gm/m^2) with leucovorin rescue compared to escalating methotrexate without leucovorin rescue (Capizzi I) during interim maintenance I.
IV. Correlate Day 29 minimal residual disease (MRD) with event-free survival (EFS) and overall survival (OS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be eligible for and enrolled on classification study COG-AALL03B1
- •Newly diagnosed B-precursor acute lymphoblastic leukemia
- •WBC > 50,000/mm^3 for patients age 1 to 9
- •Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease
- •Whit blood cell (WBC) criteria:
- •Age 1 - 9 years: WBC >= 50,000/uL
- •Age 10 - 30 years: any WBC
- •Prior steroid therapy: any WBC
- •Testicular disease: any WBC
- •Patients shall have had no other prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine
- •Patients receiving prior steroid therapy (as described in AALL03B1) are eligible for study; the dose and duration of previous steroid therapy should be carefully documented
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Patients with Down syndrome are ineligible to enroll onto this study
研究组 & 干预措施
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Pegaspargase (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Cyclophosphamide (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Cytarabine (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Dexamethasone (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Mercaptopurine (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Methotrexate (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Radiation Therapy (Radiation)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Thioguanine (Drug)
Arm I
Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Vincristine Sulfate (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Cyclophosphamide (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Cytarabine (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Dexamethasone (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Leucovorin Calcium (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Mercaptopurine (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Methotrexate (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Pegaspargase (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Radiation Therapy (Radiation)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Thioguanine (Drug)
Arm II
Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.
干预措施: Vincristine Sulfate (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Cyclophosphamide (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Cytarabine (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Dexamethasone (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Mercaptopurine (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Methotrexate (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Pegaspargase (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Prednisone (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Radiation Therapy (Radiation)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Thioguanine (Drug)
Arm III
Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Vincristine Sulfate (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Cyclophosphamide (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Cytarabine (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Dexamethasone (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Leucovorin Calcium (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Mercaptopurine (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Methotrexate (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Pegaspargase (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Prednisone (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Radiation Therapy (Radiation)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Thioguanine (Drug)
Arm IV
Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. 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 by infusion, injection, intrathecally, and by mouth for up to 8 weeks.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
时间窗: 5 years
Event Free Probability.
次要结局
- Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS).(5 years)
- Correlation of Early Marrow Response Status With MRD Negative.(Day 29)
- Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS)(5 years)
- Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS).(5 years)
- Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS)(5 Years)
- Correlation of Early Marrow Response Status With MRD Positive.(Day 29)