Moscow-Berlin 2008 Multicenter Randomised Study for Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents
试验速览
- 阶段
- 不适用
- 入组人数
- 3,000
- 试验地点
- 39
- 主要终点
- Event-free survival
研究概览
简要总结
QUESTIONS AND OBJECTIVES OF ALL-MB-2008 STUDY
- Whether the early PEG-asparaginase in induction will lead to the earlier achievement of remission, improvement of days 8 and 15 responses leading to an earlier reconstitution of bone marrow and immunocompetence, decrease of severe infections and early mortality rate?
- Whether the use of PEG-asparaginase in induction will allow to avoid the anthracyclines in standard risk group patients and to reduce treatment myelotoxicity?
- Whether the administration of 9 doses of PEG-asparaginase 1,000 U/m2 instead of 18 doses of E.coli L-asparaginase 5,000 U/m2 in standard risk patients will improve treatment outcome?
- Whether the administrations of high dose methotrexate (2 g/m2 in 24 hours) during 1-st consolidation in intermediate risk patients will result in decrease of central nervous system relapse incidence and improvement of event-free and overall survival? Whether the increase of 6-mercaptopurine starting dose up to 50 mg/m2 in 1-st consolidation phase (instead of 25 mg/m2) will decrease in relapse risk, but would not be accompanied with enhanced toxicity?
- Is it possible to completely avoid the cranial irradiation in intermediate risk patients? In some subgroup of intermediate risk patients? Is it enough to control neuroleukemia in these patients to introduce additional TIT in the consolidation phase of treatment? How will change the possible late effects in these patients according to the third arm of randomization?
- Will the new risk group stratification to improve overall and event-free survival?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at diagnosis at 1 to 18 years.
- •The start of induction therapy within a time interval of study recruitment phase.
- •The diagnosis of ALL is to be proved by the morphological, cytochemical, and immunological analysis of tumor cells in bone marrow.
- •Informed consent of the parents (guardians) of the patient to be treated in one of the clinics included in this multicenter study.
排除标准
- •ALL is a second malignant tumor;
- •The disease is a relapse of previously misdiagnosed and, therefore, inadequately treated ALL;
- •There is severe concomitant disease, which significantly impedes chemotherapy protocol (such as multiple malformations, heart diseases, metabolic disorders, etc.);
- •There is a lack of important basic data needed for the exact adherence to the cytostatic therapy according to a specific protocol of chemotherapy (differential diagnosis of acute lymphoblastic/myeloid leukemia is not possible, stratification according to risk group is not possible);
- •The patient was treated before for a long time with cytotoxic drugs;
- •There were deviations in the treatment not covered by the protocol and/or not due to side effects of treatment and/or complications of the disease
研究组 & 干预措施
Cranial irradiation
Consolidation therapy with cranial irradiation in intermediate risk group patients
干预措施: Cranial irradiation (Radiation)
Additional TIT
Consolidation therapy with additional triple intrathecal therapy (N6) and without cranial irradiation in intermediate risk group patients
干预措施: Triple intrathecal therapy (Drug)
MTX 2,000 mg/m2
Consolidation therapy with High-dose Methotrexate 2,000 mg/m2/24 h i.v. biweekly in intermediate risk group patients
干预措施: High-dose Methotrexate (Drug)
MTX 30 mg/m2
Consolidation therapy with Low-dose Methotrexate 30 mg/m2 i.m. weekly in intermediate risk group patients
干预措施: Low-dose Methotrexate (Drug)
PEG-asp 1,000 U/m2
Consolidation therapy with PEG-L-asparaginase cons 1,000 U/m2 biweekly in standard risk group patients
干预措施: PEG-L-asparaginase cons (Drug)
L-asp 5,000 U/m2
Consolidation therapy with E.coli L-asparaginase 5,000 U/m2 weekly in standard risk group patients
干预措施: E.coli L-asparaginase (Drug)
PEG-DNR+
Induction therapy without PEG-L-asparaginase and with Daunorubicin 45 mg/m2 in standard and intermediate risk group patients
干预措施: Daunorubicin (Drug)
PEG+DNR+
Induction therapy with PEG-L-asparaginase ind (1,000 U/m2 on day 3 of therapy)and daunorubicin 45 mg/m2 in standard and intermediate risk group patients
干预措施: PEG-L-asparaginase ind (Drug)
PEG+DNR+
Induction therapy with PEG-L-asparaginase ind (1,000 U/m2 on day 3 of therapy)and daunorubicin 45 mg/m2 in standard and intermediate risk group patients
干预措施: Daunorubicin (Drug)
PEG+DNR-
Induction therapy with PEG-L-asparaginase ind (1,000 U/m2 on day 3 of therapy) without daunorubicin on day 8 in standard risk group patients
干预措施: PEG-L-asparaginase ind (Drug)
结局指标
主要结局
Event-free survival
时间窗: 3 years, 5 years and 10 years after study start
overall survival
时间窗: 3 years, 5 years and 10 years after study start
cumulative incidence of relapse
时间窗: 3 years, 5 years and 10 years after study start
次要结局
- early death rate(3 years, 5 years and 10 years after study start)
- remission death rate(3 years, 5 years and 10 years after study start)
研究者
Karachunskiy Alexander
Deputy director of Research Institute of Pediatric Hematology, Oncology and Immunology
Federal Research Institute of Pediatric Hematology, Oncology and Immunology