Clinical trial NCT01966731: Realizing Effectiveness Across Continents With Hydroxyurea (REACH)
Official title: REALIZING EFFECTIVENESS ACROSS CONTINENTS WITH HYDROXYUREA (REACH): A PHASE I/II PILOT STUDY OF HYDROXYUREA FOR CHILDREN WITH SICKLE CELL ANEMIA
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Keywords: Africa
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2013-10-22
Enrollment: 635
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: After enrollment, a two-month screening phase was used to perform baseline evaluations including nutritional and infectious assessments, along with supplements and treatments as deemed necessary by local guidelines (e.g., penicillin, pneumococcal immunization, Vitamin A and albendazole/mebendazole treatment per WHO recommendations, malaria prophylaxis, and iron/folate supplementation)
Primary purpose: TREATMENT

Brief 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.

Detailed 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

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. 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)

Primary outcomes:
measure: Percentage of Participants With Dose Limiting Toxic Events
timeFrame: 3 months
Secondary outcomes:
measure: Efficacy of Hydroxyurea
timeFrame: Assessed every 4 ± 1 weeks up to 204 months
measure: Medication Adherence and the Ability for Families to Adhere to Monthly Clinic Visits Are Important Feasibility Outcomes
timeFrame: Assessed every 4 ± 1 weeks 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: Ministry of Health Mbale Regional Hospital
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Russell Ware, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tshilolo L, Tomlinson G, Williams TN, Santos B, Olupot-Olupot P, Lane A, Aygun B, Stuber SE, Latham TS, McGann PT, Ware RE; REACH Investigators. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2019 Jan 10;380(2):121-131. doi: 10.1056/NEJMoa1813598. Epub 2018 Dec 1.
citation: McGann PT, Williams TN, Olupot-Olupot P, Tomlinson GA, Lane A, Luis Reis da Fonseca J, Kitenge R, Mochamah G, Wabwire H, Stuber S, Howard TA, McElhinney K, Aygun B, Latham T, Santos B, Tshilolo L, Ware RE; REACH Investigators. Realizing effectiveness across continents with hydroxyurea: Enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa. Am J Hematol. 2018 Aug;93(4):537-545. doi: 10.1002/ajh.25034. Epub 2018 Jan 27.
citation: McGann PT, Tshilolo L, Santos B, Tomlinson GA, Stuber S, Latham T, Aygun B, Obaro SK, Olupot-Olupot P, Williams TN, Odame I, Ware RE; REACH Investigators. Hydroxyurea Therapy for Children With Sickle Cell Anemia in Sub-Saharan Africa: Rationale and Design of the REACH Trial. Pediatr Blood Cancer. 2016 Jan;63(1):98-104. doi: 10.1002/pbc.25705. Epub 2015 Aug 14.