Precision Dosing of Alemtuzumab for Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Diseases
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Percentage of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0.
研究概览
简要总结
The purpose of this study is to conduct a pilot trial of a Precision Dosing approach to alemtuzumab dosing for allogeneic hematopoietic cell transplantation of patients with non-malignant diseases. The investigators will measure the ability to use a population PK model of alemtuzumab to target patient Day 0 alemtuzumab levels to 0.15-0.6ug/mL in a pilot study of 20 patients.
详细描述
The hypothesis is that the model-informed dosing regimen will prospectively allow the precision dosing of alemtuzumab to target Day 0 levels to fall between 0.15-0.6ug/mL in greater than 80% of patients. The investigators have chosen a conservative pilot study approach, and the aim is to achieve Day 0 alemtuzumab levels between 0.15-0.6ug/mL in greater than 60% of 20 patients enrolled in this pilot study based on a Simon two-stage design as detailed below.
A Simon two-stage design (Simon, 1989) is being used. The null hypothesis that 30% of patients will achieve a Day 0 alemtuzumab level between 0.15-0.6ug/mL will be tested against a one-sided alternative that the alemtuzumab dose modification will result in 60% of patients achieving a Day 0 alemtuzumab level between 0.15-0.6ug/mL. In the first stage, 7 patients will be accrued. If there are 2 or fewer patients that achieve Day 0 alemtuzumab levels within the range of 0.15-0.6ug/mL, the study will be stopped. Otherwise, 13 additional patients will be accrued for a total of 20. The null hypothesis will be rejected if 11 or more patients achieve a Day 0 level of 0.15-0.6ug/mL within the total 20 patients. This design yields a type I error rate of 0.04 and power of 0.82 when the true response rate is 0.60. The investigators will enroll up to 30 patients in order allow for subject withdrawal, but will stop enrollment once 20 patients reach Day 0.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 6 Weeks 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are undergoing RIC HCT with alemtuzumab, fludarabine, and melphalan at CCHMC for treatment of a non-malignant disease.
- •Age ≥ 6 weeks to ≤ 30 years (at time of enrollment).
- •For the first 7 patients, patients must have a 10/10 HLA matched related or unrelated stem cell donor, or be receiving a CD34+ selected stem cell product. After the first 7 patients, any donor match may be allowed after data review by the PI and medical monitor.
排除标准
- •Patients with a history of anaphylaxis to alemtuzumab.
- •Patients who have previously received alemtuzumab and have not cleared alemtuzumab prior to the start of the preparative regimen.
- •Life expectancy less than 2 weeks.
- •Patients receiving dialysis.
- •Failure to sign informed consent and/or assent, or inability to undergo informed consent process.
- •It is not medically advisable to obtain the specimens necessary for this study.
- •Not able to tolerate subcutaneous dosing (patients with severe skin conditions such as epidermolysis bullosa).
研究组 & 干预措施
Alemtuzumab
Patients less than 15kg will be given 0.6mg/kg alemtuzumab divided over days -14, -13, and -12 (0.2mg/kg/dose).
Patients greater than 15kg will be given a 3mg "test" dose on day -14 in order to limit the first dose to no more than 3 mg per the manufacturer's recommendation. This will be followed by 0.23mg/kg/dose on days -13 and -12 (to equal a total dose of approximately 0.5-0.6mg/kg).
Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.
干预措施: Alemtuzumab (Drug)
结局指标
主要结局
Percentage of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0.
时间窗: 100 Days
次要结局
未报告次要终点