The Comprehensive Assessment of BCR-ABL1 Gene Expression and Genetic Variations by qRT-PCR and NGS Assays in Chronic Myeloid Leukemia Patients Who Are Treated With Ponatinib (CAP Study)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Dynamics of BCR-ABL1 gene expression by qRT-PCR
研究概览
简要总结
This study will evaluate whether responsiveness and adverse events (AEs) to second-line or later ponatinib treatment are associated with genetic variations as measured by real-time quantitative polymerase chain reaction (qRT-PCR) and next-generation sequencing (NGS) in patients with CML of any stage who failed prior multiple targeted therapies except ponatinib.
详细描述
Ponatinib treatment will be initiated per usual treatment procedure at 45 mg once daily p.o., which will be gradually decreased to 30 mg and 15 mg according to the predefined criteria based on responsiveness to treatment and AEs in the course of the treatment. A total of 100 subjects will be enrolled within 24 months after the first subject enrollment, and ponatinib treatment will continue for 24 months after the initial dosing of ponatinib in each enrolled subject. Routine ponatinib treatment will continue at the investigator's discretion until disease progression, the occurrence of unacceptable toxicity, subject's withdrawal of consent, or occurrence of any reason for discontinuation specified in the protocol.
All molecular analysis samples will be collected, transferred, and managed by the Catholic Leukemia Research Institute, and NGS will be performed.
<Eligibility>
- Adults with BCR-ABL1-positive CML
- Subjects who were resistant or intolerant to prior targeted therapy other than ponatinib and with an indication for ponatinib treatment according to the acceptance criteria by the Ministry of Food and Drug Safety (MFDS)
- Women of childbearing potential (WOCBP) should have a negative serum or urine pregnancy test (with a sensitivity of at least 25 IU/L or equivalent to HCG) within 24 hours before initiating ponatinib treatment
- Written informed consent to ponatinib treatment
<Outcome Measures>
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are willing to and capable of providing informed consent
- •Adults with BCR-ABL1-positive CML
- •Males and females aged 18 years and above
- •Adequate organ function
- •Subjects who were resistant or intolerant to prior targeted therapy other than ponatinib and with an indication for ponatinib treatment according to the acceptance criteria by the Ministry of Food and Drug Safety (MFDS)
- •Women of childbearing potential (WOCBP) should have a negative serum or urine pregnancy test (with a sensitivity of at least 25 IU/L or equivalent to HCG) within 24 hours before initiating ponatinib treatment
- •Female subjects who are not breastfeeding
排除标准
- •Patients who were previously treated with ponatinib
- •Patients aged below 18 years of age
- •Diagnosis of severe comorbidity at baseline
- •Any other cancers within 3 years
研究组 & 干预措施
CML patients failed to TKIs except Ponatinib
The study will involve 100 patients with BCR-ABL1-positive CML who failed to prior targeted therapy other than ponatinib. Patients receiving ponatinib 45 mg once daily as a second-line or later therapy will be enrolled.
干预措施: Ponatinib (Drug)
结局指标
主要结局
Dynamics of BCR-ABL1 gene expression by qRT-PCR
时间窗: 24 months
To explore the dynamics of BCR-ABL1 kinetics by Ponatinib
次要结局
- Type and frequency of novel genetic variations (mutations, gene expressions, CNV, INDEL, etc.)(24 months)
- Cobll1/GCA/novel gene network identification: functional tests using Western blot/Knock-down assay(24 months)
研究者
Dong-Wook Kim
professor
Eulji University Hospital