Clinical trial NCT06171217: Realizing Effectiveness Across Continents With Hydroxyurea
Official title: Realizing Effectiveness Across Continents With Hydroxyurea: A Phase I/II Prospective Trial of Hydroxyurea for Children With Sickle Cell Anemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Children
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-12-14
Enrollment: 810
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The original cohort will continue treatment per planned protocol schedule of evaluations, and a new cohort will join with consent, a 3-month screening period, and treatment per planned protocol schedule of evaluations.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of long-term Hydroxyurea treatment at MTD
timeFrame: Assessed every 6 ± 1 months up to 204 months
Secondary outcomes:
measure: Reduction of malaria incidents while on hydroxyurea at MTD.
timeFrame: Assessed every 4 ± 1 weeks, then every 3 ± 1months up to 204 months
measure: Success of PK-guided dosing of hydroxyurea
timeFrame: Assessed every 6 ± 1 months up to 204 months
Other outcomes:
Locations:
city: Luanda
country: Angola
facility: Hospital Pediátrico David Bernardino
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Centre Hospitalier Monkole
city: Kilifi
country: Kenya
facility: KEMRI/Wellcome Trust Research
city: Mbale
country: Uganda
facility: Mbale Regional Hospital
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Russell Ware, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: