Pharmacokinetics of Venetoclax in Patients With Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Area under curve (AUC) of venetoclax in Chinese population
研究概览
简要总结
Venetoclax is a treatment for chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, the pharmacokinetic data in Chinese population, as well as the change of venetoclax plasma concentration while taking CYP enzyme inducers or inhibitors, remained unknown so far. Therefore, the aim of this study is to investigate the pharmacokinetic characteristics of venetoclax.
详细描述
Venetoclax has been approved for treatment of adult patients with chronic lymphocytic leukemia (CLL). Currently, there is not enough data of CLL populations from Chinese or other Asian regarding its efficacy or adverse reactions. In the phase 3 MURANO trial (NCT02005471), only 8 Asians (2.06%) were included, while other phase 1 or phase 2 studies did not show the percentage of Asian population. According to a venetoclax population pharmacokinetic study published in 2016, which integrated 505 subjects from 8 clinical trials, concluded that race was not a covariate that affect venetoclax PK. However, only 6 Asians (1.19%) were included, and some of the subjects were small lymphocytic lymphoma (SLL), non-Hodgkin's lymphoma (NHL) or healthy volunteers.
The pharmacokinetics of venetoclax is affected by many factors, and the most influential factors may be fat content from dietary and concomitant use of CYP3A inhibitors or inducers. In particular, patients with hematological malignancies often require antifungal agents (such as voriconazole, posaconazole) as prophylaxis or treatment of fungal infections during chemotherapy. Therefore, these two factors will be considered in this study.
The most common side effect after using venetoclax is neutropenia. About 60.8% of patients developed any grades neutropenia, 43.3% required dose interruption, 8.2% required dosage reduction, and 2.6% required permanent treatment discontinuation because of neutropenia in phase 3 MURANO trial. Recent studies have found that the probability of ≥ grade 3 neutropenia and infection seems to be inversely related to the blood concentration of venetoclax, that is, the higher the blood concentration of venetoclax, the lower the probability of neutropenia and infection.
This observational study is designed to examine the plasma concentration of venetoclax in patients with CLL or AML, to create a pharmacokinetic model of venetoclax in Chinese population, and to analyze the extent to which CYP enzyme inhibitors and inducers may have effect on venetoclax plasma concentration. Moreover, the association between therapeutic effectiveness, adverse events, and venetoclax plasma concentration will also be analyzed in this study, and the final purpose is to establish the principle of clinical dose adjustment in the future.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (≥ 20 year-old) with diagnosis of chronic lymphocytic leukemia
- •Patients who meet the above criteria and have already initiated or are going to receive venetoclax treatment at National Taiwan University Hospital/National Taiwan University Cancer Center from July 2020 to December 2025
排除标准
- •Patients who are unable to cooperate with blood drawing
- •Patients who have not submit the informed consent
研究组 & 干预措施
Venetoclax
Adult CLL patients (≥ 20 year-old) who have already initiated or are going to receive venetoclax treatment at National Taiwan University Hospital/National Taiwan University Cancer Center from July 2020 to December 2025.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Area under curve (AUC) of venetoclax in Chinese population
时间窗: July 1, 2020 to December 31, 2025
Area under curve (AUC) will be calculated through multiple plasma concentrations drawn from the patients after taking venetoclax.
Clearance (CL) of venetoclax in Chinese population
时间窗: July 1, 2020 to December 31, 2025
Clearance (CL) will be calculated through multiple plasma concentrations drawn from the patients after taking venetoclax.
Half-life (T1/2) of venetoclax in Chinese population
时间窗: July 1, 2020 to December 31, 2025
Half-life (T1/2) will be calculated through multiple plasma concentrations drawn from the patients after taking venetoclax.
次要结局
- Analysis of venetoclax plasma concentration with concomitant CYP enzyme inhibitors or inducers(July 1, 2020 to December 31, 2025)
- Association between venetoclax plasma concentration and therapeutic effectiveness, adverse events(July 1, 2020 to December 31, 2025)
- Establishment of venetoclax clinical dose adjustment(July 1, 2020 to December 31, 2025)