Realizing Effectiveness Across Continents With Hydroxyurea: A Phase I/II Prospective Trial of Hydroxyurea for Children With Sickle Cell Anemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 811
- 试验地点
- 4
- 主要终点
- Efficacy of long-term Hydroxyurea treatment at MTD
研究概览
简要总结
REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 3 and 10 years of age. 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
REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 3 and 10 years of age. 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. In the REACH prospective trial, the Original Cohort will receive long-term treatment while for the New Cohort, treatment will continue at least 4 years using PK-guided dosing after an initial 3-month screening period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 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)
- •In the Original Cohort, age range of 1.00-9.99 years, inclusive, at the time of enrollment (now age 5.5 - 17.5 years); age range 3.0-10.0 years for the New Cohort
- •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.
- •Pre-existing severe hematological toxicity (temporary exclusions)
- •Anemia: Hb <4.0 g/dL
- •Anemia: Hb <6.0 g/dL with ARC <100 x 109/L
- •Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 g/dL
- •Thrombocytopenia: Platelets <80 x 109/L
- •Neutropenia: ANC <1.0 x 109/L
- •Blood transfusion within 60 days before enrollment (temporary exclusion)
- •In the Original Cohort, hydroxyurea use within 6 months before enrollment (temporary exclusion). In the New Cohort, the children should be hydroxyurea naïve, without any prior treatment exposure.
研究组 & 干预措施
Original Cohort
The original REACH cohort continuing study treatment per the protocol schedule of evaluations.
干预措施: Hydroxyurea (Drug)
New Cohort
Newly enrolled REACH participants consent, 3 months screening, and treatment per the protocol schedule of evaluations
干预措施: Hydroxyurea (Drug)
结局指标
主要结局
Efficacy of long-term Hydroxyurea treatment at MTD
时间窗: Assessed every 6 ± 1 months up to 204 months
The efficacy of hydroxyurea will be primarily assessed through fetal hemoglobin (HbF), comparing treatment with baseline values.
次要结局
- Success of PK-guided dosing of hydroxyurea(Assessed every 6 ± 1 months up to 204 months)
- Reduction of malaria incidents while on hydroxyurea at MTD.(Assessed every 4 ± 1 weeks, then every 3 ± 1months up to 204 months)