Pilot Study of Scaling Busulfan Dose to Body Surface Area in Children Undergoing Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Number of participants who achieve a therapeutic drug exposure after the first dose of Busulfan
研究概览
简要总结
The goal of this pilot study is to determine if scaling the first busulfan dose to Body Surface Area (BSA) in children with a BSA ≥0.5 m2 and using a BSA-banded dosing table for infants (BSA <0.5 m2) increases the fraction of patients achieving a therapeutic drug exposure after the first dose.
详细描述
Busulfan is a drug used in conditioning regimens for bone marrow transplantation. Busulfan levels outside the desired range can cause excessive side effects or failure of bone marrow engraftment. The initial dose of busulfan is currently scaled to body weight; on subsequent days the dose may be adjusted to achieve busulfan levels in a therapeutic range. However, only half of children receiving a busulfan dose scaled to body weight achieve therapeutic blood levels after the first dose. We performed computer simulations of alternative dosing methods for infants and children, and identified that dosing based on body surface area (BSA) could significantly increase the number of children achieving therapeutic blood levels after the first dose. This study will test whether this new dosing method results in a higher percentage of patients achieving the desired busulfan blood levels after the first dose. The study will enroll up to 38 children receiving high doses of busulfan as part of their standard conditioning regimen prior to bone marrow transplant. We will use the busulfan blood levels that are routinely measured after the first dose to determine the effectiveness of our new dosing method.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject age: ≤21 years
- •Body Surface Area (BSA):
- •Group A: BSA ≥0.5 m2
- •Group B: BSA <0.5 m2
- •Planned for once-daily busulfan-containing conditioning regimen pre-bone marrow transplant
- •Scheduled to have TDM after the first dose of busulfan
- •Diagnosis: both benign and malignant conditions are eligible
排除标准
- •1. At the time of enrollment, patients may not receive medications that significantly alter busulfan clearance, as specified below.
- •a. If patients had received the drugs listed below prior to enrollment, the following washout periods, based on ≥ 6 times drug t½, are required.
- •Deferasirox: ≥7 days Metronidazole: ≥7 days Ketoconazole, voriconazole: ≥7 days Itraconazole, posaconazole: ≥14 days Phenytoin: ≥21 days
研究组 & 干预措施
Group B
Patients receiving once daily busulfan in their pre-transplant conditioning regimen will have the first busulfan dose scaled to their BSA instead of their body weight. On day 1, patients with BSA <0.5 m2 the dose will be selected from a BSA-banded dosing table. Subsequent doses of busulfan on days 2-4 will be guided by standard care, including therapeutic drug monitoring (TDM) to achieve an AUC within the therapeutic range.
干预措施: Busulfan (BU) (Drug)
Group A
Patients receiving once daily busulfan in their pre-transplant conditioning regimen will have the first busulfan dose scaled to their BSA instead of their body weight. On day 1, patients with BSA ≥0.5 m2 will receive 100 mg/m2 Busulfan. Subsequent doses of busulfan on days 2-4 will be guided by standard care, including therapeutic drug monitoring (TDM) to achieve an AUC within the therapeutic range.
干预措施: Busulfan (BU) (Drug)
结局指标
主要结局
Number of participants who achieve a therapeutic drug exposure after the first dose of Busulfan
时间窗: 1 day
Dosing for patients in Group A (BSA \>=0.5m2) will be scaled to Body Surface Area, and patients in Group B (BSA \<0.5m2) will be dosed based on the infant dosing table for Day 1 dose. The value range for therapeutic drug exposure is 36,000 μM/min (Lower Bound) - 6,000 μM/min (Upper Bound)
次要结局
- Glutathione sample concentration over the 4-day course of busulfan administration.(4 days)
- Number of participants with sinusoidal obstruction(100 days post transplant)
- Number of participants with engraftment failure(100 days post transplant)