Safety of Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.
研究概览
简要总结
Sickle cell disease (SCD) is an inherited blood disorder that causes the red blood cells to change their shape from a round shape to a half-moon/crescent or sickled shape. People who have SCD have a different type of protein that carries oxygen in their blood (hemoglobin) then people without SCD. This different type of hemoglobin makes the red blood cells change into a crescent shape under certain conditions. Sickle-shaped cells are a problem because they often get stuck in blood vessels blocking the flow of blood, and cause inflammation and injury to the important areas in the body. Lexiscan is drug that may prevent this inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a fast infusion during a heart stress test in people who are unable to exercise enough to put stress on their heart by making it beat faster. Lexiscan has never been studied in patients with SCD and has never been given as a long infusion.
详细描述
- In this research study we are looking for the highest dose of Lexiscan that can be given safely to patients with SCD. There are 4 stages to this study. Each stage will look for the highest dose that can be given safely in the following situations: Stage 1: Lexiscan will be given through a 12 hours infusion to adults with SCD who are not having a pain crisis. Stage 2: Lexiscan will be given through a 24 hour infusion to adults with SCD who are not having a pain crisis. Stage 2b: Lexiscan will be given through a 48 hour infusion to adults with SCD who are not having a pain crisis. Stage 3: Lexiscan will be given through a 24 hour infusion to adults with SCD who are having a pain crisis. Stage 4: Lexiscan will be given through a 24 hour infusion to children with SCD who are having a pain crisis. Stages 1-3 are now complete and closed to accrual. The study is now open to children ages 10-17 with SCD pain crisis (stage 4) only.
- When participants sign the consent form, they will be told what stage they will join.
- Participants in Stages 1, 2, and 2b will be given an infusion of the study drug at the time when they do not have a pain crisis. The infusion for Stage 1 participants will be 12 hours long, followed by a 6-hour observation period. The infusion for Stage 2 will be 24 hours long, followed by a 6-hour observation period. The infusion for Stage 2b will be 48 hours long, followed by a 6-hour observation period.
- Participants in Stages 3 and 4 will be given one infusion of the study drug when they are admitted to the hospital for a pain crisis. The infusion will be 24 hours long, followed by a 6-hour observation period. During the infusion, they will receive standard treatment for their pain crisis.
- Before the infusion the following procedures will be performed: Pulmonary function test (optional, Stage 1 only), blood test and vital signs.
- During the infusion the following procedures will be performed: heart rate and amount of oxygen in the blood will be monitored continuously, blood tests and blood pressure.
- During the observation period immediately following the infusion the following procedures will be performed: heart rate and amount of oxygen in the blood will be monitored continuously, blood tests, blood pressure and Pulmonary Function test (optional, Stage 1 only).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Stage 1
12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
干预措施: Lexiscan (Drug)
Stage 2
24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
干预措施: Lexiscan (Drug)
Stage 3
24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
干预措施: Lexiscan (Drug)
Stage 4
24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
干预措施: Lexiscan (Drug)
Stage 2B
48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
干预措施: Lexiscan (Drug)
结局指标
主要结局
Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.
时间窗: 30 to 54 hours plus 30-day follow-up
Per protocol, Lexiscan was considered "safe" if well tolerated based on number of DLTs reported. Stage 1 of the study was a 3+3 dose escalation study. Three doses were tested: 0.24 mcg/kg/hr (dose level 0), 0.6 mcg/kg/hr (dose level 1), and 1.44 mcg/kg/hr (dose level 2). Dose escalation continued until 6 participants were treated at the maximum planned dose (dose level 2). We studied a total of 15 patients in Stage 1. In Stages 2 and 3, if at least 2/3 participants tolerated the dose, an additional 3 participants were studied. We studied 6 participants in each of stages 2 and 3. In stage 2b, Lexiscan was studied for a longer (48 hr) duration in 3 participants. In stage 4, Lexiscan was studied in 3 pediatric participants.
次要结局
- Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.(pre-drug to 54 hours)
- Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.(pre-drug to 54 hours)
研究者
David G. Nathan, MD
Professor of Pediatrics
Dana-Farber Cancer Institute