Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 89
- 试验地点
- 31
- 主要终点
- Event Free Survival (EFS) probability
研究概览
简要总结
The trial is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR-positive for the PML-RARα transcript and less than 18 years of age.
详细描述
Acute promyelocytic leukemia (APL) in children has become a highly curable disease with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy with an overall remission rates equal to or higher than 98% and cure rates now exceeding 80% 1-9.
Based on data coming from adults indicating that at least standard-risk APL patients may be cured without chemotherapy (i.e., with a treatment combining arsenic trioxide (ATO) and ATRA only) 10-12, this ICC APL 02 study was designed with the aim of validating the efficacy of a treatment combining:
- ATO and ATRA in newly diagnosed APL standard-risk (SR) children and adolescents and
- ATO, ATRA and gemtuzumab ozogamicin (GO) in newly diagnosed APL high-risk (HR) children and adolescents.
Following one induction course of treatment combining ATO and ATRA +/- GO depending on risk stratification, patients will receive 4 ATO/ATRA based consolidation blocks. This is the first pediatric trial delivering a non-chemotherapy-based treatment for children with APL, being the whole treatment based on the use of ATRA, ATO (and GO in HR patients). The aim of the study is to demonstrate at least an equivalent efficacy and safety of this treatment not containing cytostatic agents compared to the standard protocols combining ATRA and chemotherapy (i.e. ICC APL Study 01).
The trial is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR-positive for the PML-RARα transcript and less than 18 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed APL confirmed by the presence of PML/RARα fusion gene
- •Age <18 years
- •Written informed consent by parents or legal guardians
排除标准
- •Patients with a clinical diagnosis of APL but subsequently found to lack PML/RARα rearrangement should be withdrawn from the study and treated on an alternative protocol
- •Significant liver dysfunction (bilirubin serum levels >3 mg/dL, ALT/AST serum levels greater than 5 times the normal values)
- •Creatinine serum levels >2 times the normal value for age
- •Significant arrhythmias, EKG abnormalities (*see below), other cardiac contraindications (L-FEV <50% or LV-FS <28%)
- •Neuropathy
- •Concurrent active malignancy
- •Uncontrolled life-threatening infections
- •Pregnant or lactating female
- •Patients who had received alternative therapy (APL not initially suspected; ATRA and/or ATO not available
研究组 & 干预措施
High Risk (HR)
Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
干预措施: Arsenic Trioxide (Drug)
Standard Risk (SR)
Patient with APL and WBC less than 10x10e9/L at presentation before start treatment
干预措施: Arsenic Trioxide (Drug)
Standard Risk (SR)
Patient with APL and WBC less than 10x10e9/L at presentation before start treatment
干预措施: All-trans retinoic acid (Drug)
High Risk (HR)
Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
干预措施: Mylotarg (Drug)
High Risk (HR)
Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
干预措施: All-trans retinoic acid (Drug)
结局指标
主要结局
Event Free Survival (EFS) probability
时间窗: 3 years
SR patients: To evaluate the efficacy in terms of event-free survival of a treatment combining arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in newly diagnosed APL standard-risk children and adolescents HR patients: To evaluate the efficacy in terms of event-free survival of a treatment combining arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and gemtuzumab ozogamicin (GO) in newly diagnosed APL high-risk children and adolescents
次要结局
- Rate of hematological CR/CRi after induction(5 years)
- Probability of overall survival (OS) at 3 years(3 years)
- Total hospitalization days during therapy(5 years)
- Cumulative incidence of relapse (CIR) at 3 years(3 years)
- Incidence of hematological and non-hematological toxicity(5 years)
- Rate of molecular CR/CRi after induction(5 years)
- Rate of early death during induction(5 years)
- Rate of molecular remission after 3 consolidation cycles(5 years)
- Assessment of PML/RARα transcription level reduction during treatment(5 years)
- Pediatric Quality of Life assessment(5 years)