Population Pharmacokinetics and Pharmacodynamics of Thiotepa and TEPA in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (HCT).
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.
研究概览
简要总结
Thiotepa is a chemotherapy drug used extensively in bone marrow transplantation. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, triethylene phosphoramide (TEPA). The goal of this study is to determine what causes some children to have different drug concentrations of thiotepa and TEPA in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that certain clinical and genetic factors cause changes in thiotepa and TEPA drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
详细描述
Thiotepa is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric hematopoietic cell transplantation (HCT) to promote stem cell engraftment. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, TEPA.
This is a single-center, prospective, non-interventional pharmacokinetics (PK) study investigating the clinical pharmacology of thiotepa and TEPA in 60 children undergoing hematopoietic stem cell transplant (HCT) at University of California, San Francisco Benioff Children's Hospital. Patients would receive thiotepa regardless of whether or not they decide to consent to PK sampling.
Thiotepa doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing thiotepa and TEPA exposure in pediatric HCT recipients. Population PK methodologies support the use of sparse sampling and therefore allow the investigators to investigate drug levels in a pediatric population that would otherwise not be feasible using traditional intensive PK sampling.
Subjects will undergo PK sampling of plasma thiotepa and TEPA drug concentrations over the duration of thiotepa therapy (3 to 5 days).
To evaluate sources of variability impacting thiotepa and TEPA exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •be between 0 to 17 years of age;
- •meet protocol specific eligibility criteria for autologous or allogeneic HCT
- •will be receiving thiotepa as part of their conditioning regimen.
排除标准
- •Any child 7-17 years of age unwilling to provide assent
- •Parent or guardian unwilling to provide written consent
研究组 & 干预措施
Pediatric Hematopoietic Stem Cell Transplant Recipients
Children undergoing hematopoietic stem cell transplant (HCT) at University of California, San Francisco Benioff Children's Hospital
干预措施: Thiotepa (Drug)
结局指标
主要结局
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.
时间窗: 24 hours post start of infusion
Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance
次要结局
- Event free survival according to the AUC of thiotepa(1 year post transplant)