CML Pediatric ITK Response According to Molecular Identification at Diagnosis (CML Piramid
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Complete cytogenetic response (CCR)
研究概览
简要总结
Treatment of chronic myeloid leukemia (CML) has been revolutionized by tyrosine kinase inhibitor (TKI). Nevertheless, case of failure and suboptimal response are still observed even in children. Pediatric CML is a rare disease and differs from adult in terms of disease presentation and treatment response underlying a likely different CML biology. Molecular mechanisms that induce resistance to TKI are still poorly characterized except mutations in the tyrosine kinase domain of BCR::ABL1. We propose to search for a molecular signature to predict the response to TKI in the pediatric population.
详细描述
Commonly mutated genes associated with myeloid malignancies have been described in acceleration phase and blastic phase but also at diagnostic in adult chronic phase-CML (CP-CML). The impact of these mutations on treatment response is still debated but several studies observed a worse outcome in adult patients with some mutations. In children only one study explored the molecular status of 30 genes in 21 children and young adults. They found a higher proportion of ASXL1 mutations in children than in adult They did not observed any significant difference in overall survival of ASXL1 mutated versus non-mutated patients but probably due the small size of the cohort. We propose here, to investigate retrospectively on DNA at diagnosis of 88 CP-CML children the mutation status of 64 genes by next generation sequencing and to see if there is an association with the response to TKI treatment. We will complete the molecular signature by analyzing the differentially genetic expression profile by RNA-seq on peripheral blood RNA of 8 patients with CCR at 12 months (and/or a BCR ::ABL1 IS ≤1%IS) and 8 patients with no CCR at 12 months.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at diagnosis less than or equal to 18 years
- •Presence of a Philadelphia chromosome detected by cytogenetic analysis (conventional karyotype or Fluorescence In Situ Hybridization (FISH)) and a BCR ::ABL1 transcript e13a2 ou e14a2
- •Diagnosis in chronic phase according to the European Leukemia Net (ELN) criteria
- •First-line treatment with TKIs
- •Possible pre-treatment with hydroxyurea
- •DNA available at diagnosis
- •RNA available for a sub-group patients (8 responders vs 8 no responders)
排除标准
- •Age at diagnosis more than 18 years
- •Diagnosis in accelerated phase or blastic phase
- •First line treatment other than TKI
结局指标
主要结局
Complete cytogenetic response (CCR)
时间窗: At 12 months from TKI start
We will analyse the impact of the presence of mutations on the obtention of CCR
次要结局
- Molecular response(At 3, 12, 18 and 24 months)
- Progression Free Survival (PFS)(At 3, 12, 18 and 24 months)
- Type of response according to ELN2020 criteria(At 3, 12, 18 and 24 months)
- Occurrence of TK domain mutation(At 3, 12 18 and 24 months)
- Overall Survival (OS)(At 3, 12, 18 and 24 months)
- Occurrence of secondary resistance(At 3, 12, 18 and 24 months)