Evaluation of Treosulfan Pharmacokinetics (PK) in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 2
- 主要终点
- 1) Assess maximum concentration (Cmax) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
研究概览
简要总结
Every year around 70 children affected by cancer or life-threatening genetic diseases undergo haematopoietic cell transplantation (HCT) within the Blood and Marrow Transplant (BMT) unit at Great Ormond Street Hospital (GOSH).
One of the main goals of the BMT unit over the last decade has been to reduce the morbidity and mortality related to HCT, and the group has become a world-leader in pioneering less toxic transplants.
Fixed high doses of chemotherapy drugs are generally used to prepare children for HCT but several studies have shown a correlation between the concentration of these drugs achieved in the patient's blood, and the success or failure of the HCT procedure.
Recently a new drug, Treosulfan, has become available for use in patients undergoing HCT, and GOSH has pioneered its introduction in children undergoing HCT. With promising early results, Treosulfan has become the pre-HCT drug of choice, however, very little is currently known about how the drug is metabolised and cleared from the body, particularly in children.
The investigators therefore plan to investigate the pharmacokinetic (PK) profile of Treosulfan in children undergoing HCT at GOSH and define which parameters affect its metabolism and clearance, and what blood levels are associated with a favourable outcome (graft take without toxicity) or a poor result (graft rejection and/or toxicity).
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
- 28 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age ≥ 28 days and ≤ 18 years old;
- •Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30;
- •provide signed, written informed consent from parent or guardian;
- •be able to comply with study procedures and follow-up examinations;
- •have adequate organ function (as indicated by Table 1, page 27), within 14 days prior enrollment;
- •negative pregnancy test in post-pubertal female patients.
排除标准
- •patients aged < 28 days and > 18 years old;
- •patients with compromised organ function*;
- •patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study;
- •known hypersensitivity to Treosulfan or Fludarabine;
- •pregnancy/lactation.
研究组 & 干预措施
Treosulfan PK
Children with indication to HSCT receiving Treosulfan
干预措施: Treosulfan (Drug)
结局指标
主要结局
1) Assess maximum concentration (Cmax) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
时间窗: day -7 and day -5 pre HSCT
2) Assess half life after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
时间窗: Day -7 and day-5 pre HSCT
3) Assess the area under the curve (AUC) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
时间窗: Day -7 and day -5 pre HSCT
次要结局
- 1) Assess interindividual and intraindividual variability of PK parameters in children of different age and weight;(day -7 and -5 pre HSCT)
- 2) Assess the relationship between PK parameters and patient characteristics;(day -7 and -5 pre HSCT)
- 3) Assess the relationship between Treosulfan PK and regimen related toxicity (using the NCI toxicity criteria scoring system) and survival;(from day -7 pre HSCT to day +100 post HSCT)
- 4) Assess the relationship between Treosulfan PK and efficacy parameters, such as rate of engraftment and donor chimerism.(from day -7 pre HSCT to day + 360 post HSCT)