International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia

University Hospital Schleswig-Holstein137 个研究点分布在 4 个国家目标入组 6,136 人开始时间: 2010年6月最近更新: 2022年5月24日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方
入组人数: 6,136
试验地点: 137
主要终点: Event-free survival

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Rationale/Purpose: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia (ALL).

This trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with ALL.

Study objectives

Primary study questions:

Non high-risk (non-HR) precursor-B ALL (pB-ALL) patients with TEL/AML1-negative ALL or unknown TEL/AML1 status and flow cytometry minimal residual disease (MRD) in bone marrow on day 15 <0.1% or with TEL/AML1-positive ALL (randomized study question R1): Can the daunorubicin dose in Protocol IA be safely reduced by 50 % with a non-inferior EFS and a reduction of toxicity (treatment-related mortality and AE/SAE in Protocol I)?
Patients with pB-ALL and risk group medium risk (MR) (randomized study question R2): Can the clinical outcome be improved by protracted asparagine depletion achieved through application of intensified PEG-L-asparaginase during reintensification and early maintenance?
High-risk (HR) patients (as identified by day 33 - randomized study question RHR): Can the clinical outcome be improved by protracted exposure to PEG-L-asparaginase during Protocol IB?

Secondary study questions:

Standard risk (SR) patients identified by at least one sensitive marker: Is the clinical outcome comparable to that obtained in SR patients (identified with two sensitive markers) in AIEOP-BFM ALL 2000, or can the outcome even be improved with the use of PEG-L-asparaginase instead of native E. coli L-ASP?
T-ALL non-HR patients: Can the high level of outcome which was obtained for these patients in study AIEOP-BFM ALL 2000 be preserved or even improved with the use of PEG-L-ASP instead of native E. coli L-ASP?
HR patients with persisting high MRD levels despite the use of the HR blocks in the intensified consolidation phase "MRD Non-Responders": Is it possible to improve the outcome and to achieve a further reduction of leukemic cell burden by administration of an innovative treatment schedule (DNX-FLA)?
Patients participating in the randomized asparaginase studies (pB-ALL/MR, HR): Are asparaginase activity and asparaginase antibodies associated with development of allergic reactions, and do they have an effect on the outcome of the patients?
What is the relative value of different methods of MRD monitoring in the definition of alternative stratification systems within a BFM-oriented protocol?

详细描述

Risk Stratification

T/non-HR: T-ALL in absence of any HR criteria (see below)
pB/non-HR: pB-ALL in absence of any HR criteria (see below).
SR (polymerase chain reaction(PCR)-MRD-SR (MRD-negative on day 33 and 78) or, if no PCR-MRD result available, FCM d15 < 0.1%)
MR (no SR)
HR: Prednisone poor-response (≥1000 blast cells/µl in peripheral blood on day 8), blast cells ≥10% in bone marrow on day 15 as measured by FCM, non-remission on day 33, positivity for MLL/AF4 or t(4;11), hypodiploidy (< 45 chromosomes), PCR-MRD-HR (MRD ≥10E-3 on day 78) or PCR-MRD-MR SER (only in pB-ALL, MRD ≥ 10-3 on day 33 and MRD positive at a level of < 10E-3 on day 78)

Chemotherapy

According to the risk group, patients receive the following chemotherapy elements:

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Factorial
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

•newly diagnosed acute lymphoblastic leukemia
•age ≥ 1 year (> 365 days) and < 18 years old (up to 17 years old and 365 days)
•no Ph+ (BCR/ABL or t(9;22)-positive) ALL
•no evidence of pregnancy or lactation period
•no participation in another clinical study
•patient enrolled in a participating center
•written informed consent

排除标准

•pre-treatment with cytostatic drugs
•pre-treatment with cytostatic drugs
•steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis
•treatment started according to another protocol
•underlying diseases that prohibit treatment according to the protocol
•ALL diagnosed as second malignancy steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis