Realizing Effectiveness Across Continents With Hydroxyurea (REACH)

Sickle Cell Disease Clinical Trial

— REACH  

Official title:

REALIZING EFFECTIVENESS ACROSS CONTINENTS WITH HYDROXYUREA (REACH): A PHASE I/II PILOT STUDY OF HYDROXYUREA FOR CHILDREN WITH SICKLE CELL ANEMIA

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01966731
• Other study ID #: 2013-4221
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2014
• Est. completion date: August 2033

Study information

• Verified date: August 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

STUDY OBJECTIVES 1. 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) 2. To monitor the safety of hydroxyurea therapy, specifically documenting hematological toxicities (cytopenias) and serious infections (bacterial and malarial) 3. 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) 4. To explore the pharmacokinetic and genetic basis for any observed inter-patient variability in the clinical or laboratory response to hydroxyurea. 5. To evaluate the economic cost of providing hydroxyurea therapy in the REACH study sites. 6. To investigate the effects of hydroxyurea dose escalation on laboratory and clinical parameters

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 635
• Est. completion date: August 2033
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 10 Years

Eligibility

Inclusion Criteria

1. Pediatric patients with documented sickle cell anemia (typically HbSS supported by hemoglobin electrophoresis, complete blood count, and peripheral blood smear)

2. Age range of 1.00-9.99 years, inclusive, at the time of enrollment

3. Weight at least 10.0 kg at the time of enrollment

4. Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements

5. Willingness to comply with all study-related treatments, evaluations, and follow-up Exclusion Criteria

1. Known medical condition making participation ill-advised, (e.g., acute or chronic infectious disease, HIV, or malignancy)

2. 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)

3. Pre-existing severe hematological toxicity (temporary exclusions)

1. Anemia: Hb <4.0 gm/dL

2. Anemia: Hb <6.0 gm/dL with ARC <100 x 109/L

3. Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 gm/dL

4. Thrombocytopenia: Platelets <80 x 109/L

5. Neutropenia: ANC <1.0 x 109/L

4. Blood transfusion within 60 days before enrollment (temporary exclusion)

5. Hydroxyurea use within 6 months before enrollment (temporary exclusion)

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Hydroxyurea
Hydroxyurea will begin at 15-20 mg/kg PO daily. Six months of treatment will be given at the fixed dose, followed by another six months with dose escalation (2.5-5.0 mg/kg increments every 8 weeks) as tolerated to 20-30 mg/kg/day or MTD. The dose escalation phase will continue through the 12-month evaluation, after which hydroxyurea will continue in maintenance phase until the common treatment termination date. The daily dose will be calculated using available capsule sizes and a goal of 15-20 (17.5 ± 2.5) mg/kg/day based on weight. After 6 months of treatment, hydroxyurea will be titrated according to myelosuppression, and will be increased to 20-30 mg/kg/day or the maximum tolerated dose (MTD). Hydroxyurea dose escalation will occur in 5.0 ± 2.5 mg/kg/day increments.

Locations

Country	Name	City	State
Angola	Hospital Pediátrico David Bernardino	Luanda
Congo, The Democratic Republic of the	Centre Hospitalier Monkole	Kinshasa
Kenya	KEMRI/Wellcome Trust Research	Kilifi
Uganda	Ministry of Health Mbale Regional Hospital	Mbale

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Countries where clinical trial is conducted

Angola,  Congo, The Democratic Republic of the,  Kenya,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxic Events	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.	3 months
Secondary	Efficacy of Hydroxyurea	The efficacy of hydroxyurea will be primarily assessed through fetal hemoglobin (HbF), comparing treatment with baseline values. Additional measures of laboratory efficacy will include changes in Hb, MCV, WBC, ANC, ARC, and bilirubin. Clinical events such as vaso-occlusive pain will be captured as secondary outcomes.	Assessed every 4 ± 1 weeks up to 204 months
Secondary	Medication Adherence and the Ability for Families to Adhere to Monthly Clinic Visits Are Important Feasibility Outcomes	Hydroxyurea treatment will be dispensed only 35 days at a time, requiring a clinic visit every 4 ± 1 weeks. 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