Thymoglobulin® Pharmacokinetics for Graft-versus Host Disease in Children and Adults Undergoing Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Area under the concentration-time curve (AUC)
研究概览
简要总结
Thymoglobulin is widely applied as serotherapy in order to prevent acute graft-versus-host disease (GvHD) and graft rejection in patients undergoing non-Human Leukocyte Antigen (HLA)-identical hematopoietic stem cell transplantations (HSCT), with a delicate balance between prevention of GvHD and the promotion of immune reconstitution. Thymoglobulin is known as a drug with high pharmacokinetic (PK) variability. This variability influences drug exposure, which in turn determines the drug response of pharmacodynamics (PD). In order to maintain efficacy while reducing adverse effects of drugs across the entire age range, identification of the PK/PD relationships and the effect of growth and maturation on the different PK and PD parameters involved are crucial.
The investigators hypothesise that a better knowledge of Thymoglobulin PK and its covariates would help to individualise dosage regimen and would improve clinical outcomes, such as GvHD and immune reconstitution.
The investigators aim to build a population PK model of Thymoglobulin in order to study PK variability and its covariates. This model will help in optimizing dosage regimen in an individually way.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient receiving Thymoglobulin therapy as part of a first HSCT
- •Age ≥ 2 years
- •Lansky or karnofsky score ≥ 50%.
- •Enrolled in a social security plan
- •Patient 18 years of age or older who is informed and has consented to participate in the study or minor patient whose parents/guardians have been informed and have given consent for the minor patient to participate in the study
- •Female patients of childbearing potential must have an effective method of contraception (a pregnancy test will also be performed at inclusion).
排除标准
- •Patient having received serotherapy (Thymoglobulin® or other) within 3 months before this HSCT
- •Patient receiving another serotherapy during conditioning (Campath®)
- •Patients with uncontrolled acute or chronic infections for which any form of immunosuppression would be contraindicated
- •Known hypersensitivity to Thymoglobulin®.
- •Pregnant or lactating women
- •Patient participating simultaneously in another study of an investigational drug (no exclusion period)
- •Patient under legal protection or deprived of liberty
研究组 & 干预措施
Experimental treatment arm
Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.
干预措施: Thymoglobulin 25 milligrams (mg) Injection (Drug)
Experimental treatment arm
Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.
干预措施: blood test (Biological)
结局指标
主要结局
Area under the concentration-time curve (AUC)
时间窗: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Measure of the Thymoglobulin® exposure by the PK criteria : Area under the concentration-time curve (AUC) . AUC is measured by day since the first day of Thymoglobulin infusion during conditioning (day 0) until elimination tf the drug. AUC is expressed as milligrams/hour/Liter. (mg/h/L)
次要结局
- Objective function value (OFV)(until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation))
- Coefficient of variation of AUC(until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation))