NCT04822532招募中不适用
Implementing Pharmacogenetics in the Busulfan Dosing Method for Children Undergoing Hematopoietic Stem-cell Transplantation: a Prospective, Multicentric, Randomized Clinical Trial
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Accuracy of the first-dose Bu area under the curve (AUC) prediction
研究概览
简要总结
The objective of this clinical trial is to evaluate the personalization the conditioning regimen prior to the hematopoietic stem cell transplant (HSCT) in children and adolescents, to improve HSCT efficacy while reducing conditioning-related toxicities. Namely, we are going to compare the accuracy of two methods for determining the first dose of busulfan, one of the medicines used during the conditioning regimen. First doses will be determined based either only on anthropometric information such as age and weight or by adding a genetic factor that influences the individual ability of busulfan metabolization.
详细描述
Participants will be randomly assigned (1:1 ratio, stratified by conditioning regimen - the presence of fludarabine) to receive their first dose of busulfan according to:
- the most performing method based on age and weight - McCune's model (control arm)
- a method that also considers a pharmacogenetic factor (variants occurring in the promoter region of the GSTA1 gene) in association with the co-administered chemotherapeutic agent fludarabine in the dose personalization (experimental arm)
This is an international study being carried out in five countries (Canada, Italy, Switzerland, France, and Denmark).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be aged from 0-18 years old on entry to the study;
- •Clinical indication of allogeneic or autologous hematopoietic stem cell transplantation;
- •The conditioning protocol must include IV Bu formulations, Busulfex® (Otsuka Pharmaceutical), Busilvex® (Pierre Fabre Pharma) or other European Medicines Agency (EMA) or Food and Drugs Administration (FDA) approved generic formulations regardless of the administration schedule (q6h, q12h, or q24h)
- •The expected length of time from recruitment to starting the conditioning regimen must be superior to 10 days;
- •Informed written consent to participate in the study signed by the participant/parent
排除标准
- •At least one of the drugs listed below scheduled to be administered in the Bu administration days up to 24h after the last dose of Bu, whenever a washout is not possible:
- •Metronidazol (required washout: 7 days)
- •Nalidixic acid (required washout: 7 days)
- •Phenytoin (required washout: 21 days)
- •Itraconazole (required washout: 14 days)
- •Ketoconazole (required washout: 7 days)
- •Voriconazole (required washout: 7 days)
- •Deferasirox (required washout: 7 days)
结局指标
主要结局
Accuracy of the first-dose Bu area under the curve (AUC) prediction
时间窗: 1 month
Proportion of the first doses which result in AUCs within the therapeutic target range defined by the prescriber
Dose adjustment requirement
时间窗: 1 month
Change in percentage between the first dose administered and the next time-wise adjustable dose: 2nd (Bu q24h), 3rd (Bu q12h), or 5th (Bu q6h) doses
Accuracy of the Bu Clearance prediction
时间窗: 1 month
Absolute prediction error between the predicted and measured Bu clearance of the first dose
次要结局
- Time to deliver the personalized dose(1 week)
- Incidence of primary and secondary graft failure(12 months)
- Overall survival(12 months)
- Incidence of treatment-related toxicities (TRTs)(12 months)
- Incidence and severity of sinusoidal obstruction syndrome (SOS)(12 months)
- Incidence and severity of acute graft-versus-host disease (aGVHD)(12 months)
- Event-free survival(12 months)
研究者
Marc Ansari
Professeur Marc Ansari
University Hospital, Geneva
研究点 (1)
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