Detecting Expression Profiles Associated With Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukaemia Patients Without Detectable Tyrosine Kinase Domain Mutations, Using Transcriptomics
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Success identification of at least 5 markers of resistance in patients without a TKD mutation and confirmation of their expression levels using qPCR
研究概览
简要总结
Chronic myeloid leukaemia (CML) is a haematological malignancy primarily driven by the fusion oncogene BCR-ABL1, resulting in a constitutively expressed tyrosine kinase. CML is treated very effectively by the tyrosine kinase inhibitors (TKIs) resulting in almost undetectable levels of disease. However, some patients show resistance to first line treatment, requiring second and third generation TKIs. Such resistance is due to the presence of tyrosine kinase domain (TKD) mutations, however TKDs do not appear to be present in all patients who do not respond to treatment.
The aim of this project is to utilise gene expression arrays to identify transcriptomic profiles associated with resistance to TKIs in the absence of a demonstrable TKD mutation. The presence of such profiles may allow for a more targeted approach to treatment, if non-responders can be identified earlier in the disease management pathway. Being able to predict those that will not respond to first line treatment will allow for better stratification of patients.
详细描述
The aim of this project is to use gene expression microarrays to detect expression profiles which may be associated with TKI resistance in order to better stratify CML patients and allow a more targeted approach to therapy. The project may also help elucidate the mechanism of resistance in those without a discernible TKD mutation. Ultimately it is hoped that this would lead to larger studies which could improve the clinical pathway for CML patients without TKD mutations.
Some previous studies have studied the gene expression profile of CML patients demonstrating resistance to TKIs, using Affymetrix arrays. However, none of these appear to have specifically investigated non-responders with and without a TKD mutation.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 17 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CML patients with poor response to TKIs as identified through routine clinical testing at SDGS, either with or without a tyrosine kinase domain mutation as tested for by mutational analysis.
排除标准
- •Any samples that do not meet the above inclusion criteria, but particularly not CML patients with an optimal response to TKIs.
结局指标
主要结局
Success identification of at least 5 markers of resistance in patients without a TKD mutation and confirmation of their expression levels using qPCR
时间窗: 2 months
次要结局
未报告次要终点