A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 2,044
- 试验地点
- 6
- 主要终点
- Incidence of directly asparaginase-related severe toxicities (Grade ≥ 3 as assessed by CTCAE v4.0) observed during induction therapy
研究概览
简要总结
A still major question in the field of acute lymphoblastic leukemia (ALL) in children - an extremely heterogeneous disease though curable in 80-90% of children and 70-80% of the adolescents - is the optimal use of L-asparaginase (ASNase). It is known that administering ASNase results in the depletion of asparagine circulating in the blood, which starves the leukemic cells and results in their death. But indeed the use of ASNase varies between protocols considering the different brands, the dose and the administration modalities. Oncaspar (PEGylated E. coli asparaginase, pegaspargase) was thus developed with the goal of reducing the immunogenicity of the native ASNase.
This is a French prospective multicentric cohort study of children and adolescents with ALL, stratified on (i) the type of ALL ( B vs T) and (ii) the anticipated risk (stratified in 3 groups for childhood B-cell precursor (BCP)-ALL and 2 groups for T-cell ALL).
It aims to answer to two different issues:
- Randomized question: what is the best way to administer pegaspargase? A cohort of children and adolescents with standard or medium risk ALL will be randomized to receive during induction either one infusion of ONCASPAR® 2500 IU/m2 at D12 or two infusions of ONCASPAR® at 1250 IU/m2 each at D12 and D26. Patients will then receive 2500 IU/m2 or 1250 IU/m2 per dose during consolidation and delayed intensification according to the initial arm of randomization.
- Non randomized question: In the High/Very High Risk groups, a non randomized intensification of the scheme of asparaginase administration is proposed during induction therapy: 2 infusions of 2500 IU/m2/day (D12 and D26) will be administered. All patients will receive 2500 IU/m2 per dose during consolidation and delayed intensifications.
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
- •Children and adolescents Age > 12 months but < 18 yearsB-lineage or T- lineage ALL
- •Written informed consent obtained before day 8 of treatment
- •Non inclusion criteria:
- •L3 (Burkitt's leukemia) (LMB type protocols)
- •Mixed Phenotype Acute Leukemia (WHO criteria).
- •Infant ALL (age ≤ 365 days (Interfant 06 protocol)
- •Secondary leukemia
- •Patients previously treated with chemotherapy (steroid exposed patients can be included and stratified according to Section 3.5) Known allergy to pegylated products
- •Pregnancy. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant must have a negative serum pregnancy before inclusion and a reliable contraception except oral contraceptives. The contraception should be maintained throughout the study and for 3 months after treatment discontinuation.
- •Known HIV positivity
- •CNS thrombosis during Prophase
排除标准
- •Ph+/BCR-ABL ALL (ESPhALL protocol)
- •CNS thrombosis before D12
研究组 & 干预措施
Arm 1
pegaspargase 2500 IU/m2 x 1: infusion of a conventional dose of pegaspargase during induction therapy: 2500 IU/m2x1
干预措施: pegaspargase 2500 IU/m2 x 1 (Drug)
Arm 2
pegaspargase 1250 IU/m2 x 2: fractionation of the 2500 IU/m2 pegaspargase dose in two infusions of 1250 IU/m2 each during delayed intensification
干预措施: pegaspargase 1250 IU/m2 x 2 (Drug)
结局指标
主要结局
Incidence of directly asparaginase-related severe toxicities (Grade ≥ 3 as assessed by CTCAE v4.0) observed during induction therapy
时间窗: Between Day 12 of induction and Day 8 of consolidation
Incidence of severe toxicities (Grade ≥ 3) directly asparaginase-related (CNS thrombosis, pancreatitis, anaphylaxis, and hyperbilirubinemia) between Day 12 and Day 49 of treatment and anyway before Day 8 of consolidation
Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 33 of induction therapy
时间窗: Day 33
asparaginase activity \> 100 IU/L
次要结局
- Percentage of patients without switch to Erwinia asparaginase(First 6-9 months)
- Percentage of patients receiving more than 95% of the intended dose of asparaginase(First 6-9 months)
- Morphological Complete Remission (CR) rates(Day 35-Day 42)
- Minimal Residual Disease (MRD)(Day 35-Day 42, Day 65-Day 105)
- Incidence of antibodies against asparaginase, measured in serum(Day 4 of delayed intensification)
- Incidence of asparagine depletion measured in plasma by a concentration below the Limit of Quantification (LOQ) of 0.4 micromol/L(Day 40 of induction)
- Incidence of adequate (> 100 IU/L) asparaginase activity measured in the plasma at day 40 of induction therapy(Day 40 of induction)
- Incidence of silent inactivation(First 6-9 months)
- Cumulative Incidence of relapses(5 years)
- Cumulative Incidence of relapse according to site of relapse(5 years)
- All other adverse events related to asparaginase(within the first 7 weeks (Day 49) of treatment and anyway before Day 8 of consolidation)
- Late adverse events related to asparaginase(after Day 49 of induction or anyway at Day 8 of consolidation or after)