Realizing Effectiveness Across Continents With Hydroxyurea

Sickle Cell Disease Clinical Trial

— REACH  

Official title:

Realizing Effectiveness Across Continents With Hydroxyurea: A Phase I/II Prospective Trial of Hydroxyurea for Children With Sickle Cell Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06171217
• Other study ID #: 2013-4221b
• Secondary ID: U01HL133883
• Status: Recruiting
• Phase: Phase 2
• Start date: October 27, 2023
• Est. completion date: October 4, 2033

Study information

• Verified date: December 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Russell Ware, MD, PhD
• Phone: 513-803-4597
• Email: russell.ware[@]cchmc.org
• 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 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 822
• Est. completion date: October 4, 2033
• Est. primary completion date: October 4, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years 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. 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

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.

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

1. Anemia: Hb <4.0 g/dL

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

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Children
• Sickle Cell Disease

Intervention

Drug:
• Hydroxyurea
Hydroxyurea, approximately 20-30 mg/kg/day, with modifications for toxicity or for mild marrow suppression
• Hydroxyurea
Hydroxyurea 15-35 mg/kg/day based on PK-guided dosing, with modifications for toxicity for mild marrow suppression

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	Mbale Regional Hospital	Mbale

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of long-term Hydroxyurea treatment at MTD	The efficacy of hydroxyurea will be primarily assessed through fetal hemoglobin (HbF), comparing treatment with baseline values.	Assessed every 6 ± 1 months up to 204 months
Secondary	Reduction of malaria incidents while on hydroxyurea at MTD.	Clinical malaria infections to identify associations of risk or protection comparing treated and untreated incidents.	Assessed every 4 ± 1 weeks, then every 3 ± 1months up to 204 months
Secondary	Success of PK-guided dosing of hydroxyurea	Fetal Hemoglobin changes from hydroxyurea at MTD	Assessed every 6 ± 1 months up to 204 months