Busulfan Pharmacokinetic Analysis and GST Pharmacogenetic Profile in Adults Undergoing Hematological Stem Cell Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 63
- 主要终点
- If GST and ABCB1 genes modify busulfan pharmacokinetics in AML patients who will be transplanted
研究概览
简要总结
The correlation between Busulfan Pharmacokinetics in AML transplanted patients and their GST (A1,T1,M1 and P1), MDR-1 genetic profile. If a pre-genetic testing of those genes can be utilized as biomarkers of SOS and/or HGVHD. This study is not an interventional study it is only checking the GST gene and MDR-1 gene
详细描述
BU levels are largely unpredictable, patients are often exposed to the toxic effects of inappropriate drug regimens before dose modifications can be made. Although the importance of TDM cannot be over emphasized, it entails trial and error and does not allow for pre- treatment dose optimization. This study, which provides an integration of genetic and pharmacokinetic data analysis of patients preconditioned for HSCT with high dose oral BU, aims to define biomarkers predictive of poor BU metabolism and clearance to prevent potential drug toxicity.This study is not an interventional study, only investigates the GST and MDR-1 genes in correlation with the "routine" Busulfan AUC done during the preparative regimen in HSCT for AML patients.
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 67 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute Myeloid Leukemia who are clinically selected for HSCT according to known protocols.
排除标准
- •Unable to give informed consent
结局指标
主要结局
If GST and ABCB1 genes modify busulfan pharmacokinetics in AML patients who will be transplanted
时间窗: end of BMT transplantation
If individuals diagnosed with AML carrying the GSTP1 variant allele rs1695 (heterozygotes) are at risk of developing supra-therapeutic BU AUC due to lower BU clearance, and if combined polymorphisms in GSTM1 and ABCB1 (3435 or 2677) are associated with BU clearance rates and AUC.
次要结局
未报告次要终点
研究者
N_Krivoy
Director Clinical Pharmacology Unit
Rambam Health Care Campus