The Value of Dexamethasone Versus Prednisolone During Induction and Maintenance Therapy of Prolonged Versus Conventional Duration of L-Asparaginase Therapy During Consolidation and Late Intensification, and of Corticosteroid + VCR Pulses During Maintenance in Acute Lymphoblastic Leukemia and Lymphoblastic Non-Hodgkin Lymphoma of Childhood
试验速览
- 阶段
- 3 期
- 入组人数
- 1,500
- 试验地点
- 23
- 主要终点
- Event-free survival after first randomization
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy plus steroid therapy is more effective for acute lymphoblastic leukemia or lymphoblastic non-Hodgkin's lymphoma.
PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus steroid therapy in treating children who have acute lymphoblastic leukemia or lymphoblastic non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
- Compare the value of dexamethasone (DM) vs prednisolone (PRDL) administered during induction therapy, in terms of event-free and overall survival, in children with acute lymphoblastic leukemia (ALL) or lymphoblastic non-Hodgkin's lymphoma (LNHL).
- Assess the value of increasing the number of administrations of asparaginase during consolidation and late intensification therapy, in terms of disease-free and overall survival, in children without very high-risk (VHR) features.
- Compare the response rate in children treated with prephase therapy comprising DM vs PRDL and intrathecal methotrexate.
- Compare the incidence and grade of toxic effects of these treatment regimens in these children.
- Compare the long-term effects of these treatment regimens on growth and pubertal development, neurocognitive, cardiac, and endocrine function, and incidence of aseptic bone necrosis in these children.
- Evaluate the proportion of children with VHR disease when defined according to extended VHR criteria, and assess the prognostic importance of the new VHR features (cytogenetics and minimal-residual disease).
- Compare the feasibility of the VHR chemotherapy protocol in patients treated with DM vs PRDL.
OUTLINE: This is a randomized, multicenter study. Patients are stratified for prephase therapy according to center, disease (acute lymphoblastic leukemia [ALL] vs non-Hodgkin's lymphoma [NHL]), WBC for ALL patients (less than 10,000/mm^3 vs 10,000/mm^3 to less than 100,000/mm^3 vs greater than 100,000/mm^3), stage for NHL patients (I or II vs III or IV), and whether prephase already started (yes vs no). Patients are stratified for protocol II therapy according to center, risk group (very low risk [VLR] vs average risk 1 [AR1] vs average risk 2 [AR2]), and treatment arm at first randomization.
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Prephase: Patients are randomized to 1 of 2 treatment arms
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Arm I: Patients receive oral prednisolone (PRDL) twice daily or methylprednisolone IV over 1 hour every 12 hours on days 1-7.
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Arm II: Patients receive dexamethasone (DM) orally twice daily or IV over 1 hour every 12 hours on days 1-7.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed acute lymphoblastic leukemia (ALL) of FAB L1 or L2 morphology
- •Positive SIg allowed OR
- •Histologically confirmed precursor B or precursor T lymphoblastic non-Hodgkin's lymphoma (NHL)
- •No diffuse large cell B-cell lymphoma, Burkitt's lymphoma, or high-grade B-cell lymphoma (Burkitt-like)
- •Very low-risk (VLR) patients meeting 1 of the following criteria:
- •ALL of B-cell lineage
- •WBC less than 10,000/mm^3
- •Must meet 1 of the following conditions:
- •DNA index greater than 1.16 and less than 1.50 and chromosome number 51-66 or unknown
- •DNA index not assessed and chromosome number 51-66
- •DNA index greater than 1.16 and less than 1.50 and chromosome number is unknown
- •Good response to prephase therapy
- •Absence of t(9;22) or BCR/ABL, t(4;11)/MLL-AF4, or 11q23/MLL rearrangement
- •No acute undifferentiated leukemia (AUL)
- •No CNS or gonadal involvement
- •Precursor B-lymphoblastic NHL stage I or II OR
- •Average risk (AR) patients:
- •Must meet 1 of the following criteria:
- •ALL with good response to prephase therapy who are neither VLR or very high risk (VHR)
- •VLR ALL with CNS involvement (CSF positive or negative)
- •Precursor B-lymphoblastic NHL stage III or IV without any VHR feature
- •Precursor T-lymphoblastic NHL
- •AR patients substratified in:
- •AR1: B-cell lineage ALL with WBC less than 100,000/mm^3
- •Surreptitious or hemorrhagic CSF becoming negative at D4 of prephase therapy
- •Precursor B-lymphoblastic NHL stage III or IV
- •Precursor T-lymphoblastic NHL stage I or II
- •AR2: B-cell lineage ALL with WBC at least 100,000/mm^3
- •T-cell lineage ALL regardless of the WBC
- •Overt or non-equivocal CNS involvement at D0 or any CSF involvement at D4
- •Gonadal involvement
- •Precursor T-lymphoblastic NHL stage III or IV
- •Newborn Down syndrome patients with AR2 features are assigned to the AR1 group OR
- •VHR patients:
- •Must meet 1 of the following criteria:
- •ALL patients meeting 1 of the following conditions:
- •Poor response to prephase therapy (at least 1,000/mm^3 blasts in peripheral blood after completion of prephase therapy)
- •t(9;22) or BCR/ABL
- •t(4;11)/MLL-AF4 = 11q23/MLL rearrangement
- •Near haploidy (no more than 34 chromosomes or DNA index less than 0.7)
- •Hypodiploid (35-40 chromosomes or DNA index 0.7 to 0.8)
- •For B lineage ALL: failure to achieve complete response (CR) after completion of protocol IA
- •For T lineage ALL: failure to achieve CR or good partial response (GPR) after completion of protocol IA
- •Minimal-residual disease (greater than 1,000 blasts/100,000 mononuclear bone marrow cells) at evaluation of IA (day 35)
- •NHL patients who failed to achieve CR or GPR after completion of protocol IA
- •All VHR patients are eligible for stem cell transplantation except those whose sole VHR criterion is a poor response to prephase therapy and who have none of the following features:
- •T-cell immunophenotype
- •Early B ALL (CD10 negative)
- •WBC at least 100,000/mm^3
- 另有 21 项未显示
排除标准
- 未提供
结局指标
主要结局
Event-free survival after first randomization
Disease-free survival after second and third randomization
次要结局
- Overall survival
- Response to prephase as assessed by number of blasts/mm³ in peripheral blood (< 1,000 vs ≥ 1,000) after randomization
- Response as assessed by bone marrow (BM) blasts after first randomization, at evaluation of prephase, and on day 15 of induction
- Toxicity and long-term toxicity as assessed by CTC v2