Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 501
- 试验地点
- 2
- 主要终点
- Overall Event-free Survival (EFS)
研究概览
简要总结
The primary objective is to estimate the overall event-free survival of children at least one year of age at diagnosis who are treated with risk-directed therapy and to monitor the molecular remission induction rate.
详细描述
These are the following secondary objectives:
- To determine if CNS irradiation can be safely omitted in the context of the systemic therapy used in the protocol.
- To identify whether prolonged (24 hour) intravenous infusions of HDMTX produce greater methotrexate polyglutamate (MTXPG) accumulation than short (4 hour) infusions 42 hours after 1 gm/m2 of HDMTX, stratified for lineage (T- vs B-lineage) and ploidy (hyperdiploid vs non-hyperdiploid B-lineage).
- To determine whether prolonged (24 hour) intravenous infusions of HDMTX produce greater antileukemic effects than short (4 hour) infusions, based on the inhibition of de novo purine synthesis in bone marrow blasts and the decrease in circulating blasts during the 4 day "window" prior to initiation of conventional remission induction therapy.
- MRD
- Other exploratory objectives
Details of Treatment Plan
Treatment will consist of three main phases, Remission Induction, Consolidation, and Continuation. Treatment with an Upfront HDMTX Window for research purposes will be optional.
All patients will receive IT therapy on day 1, dose is age dependent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of non-B-cell ALL by immunophenotyping, as determined by the reactivity pattern to a panel of monoclonal antibodies with flow cytometry as well as morphology and cytochemical staining.
- •Age range: 1 to 18 years (inclusive).
排除标准
- •Previously treated with chemotherapy for one week or longer.
研究组 & 干预措施
1
干预措施: chemotherapy, intrathecal chemotherapy (Procedure)
1
干预措施: Mercaptopurine, Imatinib (Drug)
1
干预措施: Prednisone, Dexamethasone, Vincristine, Daunorubicin (Drug)
1
干预措施: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase (Drug)
1
干预措施: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide (Drug)
1
干预措施: steroid therapy, hematopoietic stem cell transplantation (Procedure)
2
干预措施: Prednisone, Dexamethasone, Vincristine, Daunorubicin (Drug)
2
干预措施: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase (Drug)
2
干预措施: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide (Drug)
2
干预措施: Mercaptopurine, Imatinib (Drug)
2
干预措施: chemotherapy, intrathecal chemotherapy (Procedure)
2
干预措施: steroid therapy, hematopoietic stem cell transplantation (Procedure)
结局指标
主要结局
Overall Event-free Survival (EFS)
时间窗: Median follow-up time (range) 5.6 (1.3 to 8.9) years
EFS was measured from the start of on-study to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Failure to enter remission was considered an event at time zero. Measurement was determined by Kaplan-Meyer estimate.
Continuous Complete Remission Since Week 56 Therapy.
时间窗: Median follow up time (range) 4.5 (1 to 7.8) years
CCR was measured from end of week 56 therapy to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Measurement was determined by Kaplan-Meyer estimate.
次要结局
- Circulating Leukemia Cells in Peripheral Blood Change From Prior to the Methotrexate Infusion to Three Days After Between Two Arms (4 Hours vs. 24 Hours)(Immediately before the methotrexate infusion and three days after subsequent infusion)
- Minimal Residual Disease (MRD)(End of Induction (Day 46 MRD measurement))
- Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours).(42 hours after start of high dose methotrexate infusion (HDMTX))