REALIZING EFFECTIVENESS ACROSS CONTINENTS WITH HYDROXYUREA (REACH): A PHASE I/II PILOT STUDY OF HYDROXYUREA FOR CHILDREN WITH SICKLE CELL ANEMIA
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 635
- 试验地点
- 5
- 主要终点
- Percentage of Participants With Dose Limiting Toxic Events
研究概览
简要总结
REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for for pediatric patients with sickle cell anemia (SCA). The short-term goal is to obtain critical pilot data regarding the feasibility, safety, and benefit of hydroxyurea for children with SCA in multiple distinct research settings in Africa. Based on that information, the longer-term goal is to make hydroxyurea more widely available for children with SCA in Africa, particularly those identified with SCA through expanded newborn screening programs.
详细描述
STUDY OBJECTIVES
- To assess the feasibility of conducting a prospective research study using hydroxyurea therapy for SCA in sub-Saharan Africa (including adherence to monthly clinic visits and laboratory assessments, and medication compliance)
- To monitor the safety of hydroxyurea therapy, specifically documenting hematological toxicities (cytopenias) and serious infections (bacterial and malarial)
- To evaluate the benefits of hydroxyurea therapy, using both laboratory (e.g., fetal hemoglobin, hemoglobin, white blood cell count) and clinical parameters (e.g., pain, hospitalization, growth)
- To explore the pharmacokinetic and genetic basis for any observed inter-patient variability in the clinical or laboratory response to hydroxyurea.
- To evaluate the economic cost of providing hydroxyurea therapy in the REACH study sites.
- To investigate the effects of hydroxyurea dose escalation on laboratory and clinical parameters
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric patients with documented sickle cell anemia (typically HbSS supported by hemoglobin electrophoresis, complete blood count, and peripheral blood smear)
- •Age range of 1.00-9.99 years, inclusive, at the time of enrollment
- •Weight at least 10.0 kg at the time of enrollment
- •Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements
- •Willingness to comply with all study-related treatments, evaluations, and follow-up
排除标准
- •Known medical condition making participation ill-advised, (e.g., acute or chronic infectious disease, HIV, or malignancy)
- •Acute or chronic severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or height for age >3 z-scores below the median WHO growth standards, as defined in Appendix I)
- •Pre-existing severe hematological toxicity (temporary exclusions)
- •Anemia: Hb <4.0 gm/dL
- •Anemia: Hb <6.0 gm/dL with ARC <100 x 109/L
- •Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 gm/dL
- •Thrombocytopenia: Platelets <80 x 109/L
- •Neutropenia: ANC <1.0 x 109/L
- •Blood transfusion within 60 days before enrollment (temporary exclusion)
- •Hydroxyurea use within 6 months before enrollment (temporary exclusion)
研究组 & 干预措施
Hydroxyurea
After patient enrollment, a two-month pre-hydroxyurea evaluation phase will be used to perform baseline evaluations including nutritional and infectious assessments, and to provide supplements or treatments as deemed necessary. After the pre-hydroxyurea evaluation and supplementation phase, hydroxyurea dosing will be administered as a single daily dose, using capsules provided as a monthly supply in 200mg, 300mg, 400mg, or 500mg sizes.
干预措施: Hydroxyurea (Drug)
结局指标
主要结局
Percentage of Participants With Dose Limiting Toxic Events
时间窗: 3 months
An expected toxicity rate of 20% and acceptable toxicity rate of 30% were used for statistical calculations. After 53 participants at each site complete 3 months of therapy, if ≤ 15 participants have hematologic toxicity there is no early evidence against safety. If ≥ 15 of the initial participants experience toxicity, this is early evidence against safety. Future participants will begin at a lower dose of hydroxyurea (10 ± 2.5 mg/kg), with another 53 participants recruited of the same safety analysis. Upon final analysis of 133 participants at the same starting dose, safety for fixed-dose hydroxyurea can be concluded.
次要结局
- Efficacy of Hydroxyurea(Assessed every 4 ± 1 weeks up to 204 months)
- Medication Adherence and the Ability for Families to Adhere to Monthly Clinic Visits Are Important Feasibility Outcomes(Assessed every 4 ± 1 weeks up to 204 months)