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Realizing Effectiveness Across Continents With Hydroxyurea (REACH) (REACH)

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ClinicalTrials.gov Identifier: NCT01966731
Recruitment Status : Active, not recruiting
First Posted : October 22, 2013
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 12 months 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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Hydroxyurea Phase 1 Phase 2

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 investigate the effects of hydroxyurea dose escalation on laboratory and clinical parameters

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 635 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Realizing Effectiveness Across Continents With Hydroxyurea (REACH): A Phase I/II Pilot Study Of Hydroxyurea For Children With Sickle Cell Anemia
Study Start Date : June 2014
Estimated Primary Completion Date : August 2033
Estimated Study Completion Date : August 2033

Resource links provided by the National Library of Medicine

Drug Information available for: Hydroxyurea

Arm Intervention/treatment
Experimental: Hydroxyurea
After patient enrollment, a two-month pre-hydroxyurea evaluation phase will be used to perform baseline evaluations including nutritional and infectious assessments, and to provide supplements or treatments as deemed necessary. After the pre-hydroxyurea evaluation and supplementation phase, hydroxyurea dosing will be administered as a single daily dose, using capsules provided as a monthly supply in 200mg, 300mg, 400mg, or 500mg sizes.
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.
Other Names:
  • Hydrea
  • Droxia




Primary Outcome Measures :
  1. Safety [ Time Frame: 48 months ]
    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 for the same safety analysis. Upon final analysis of 133 participants at the same starting dose, safety for fixed-dose hydroxyurea can be concluded.


Secondary Outcome Measures :
  1. Efficacy [ Time Frame: 4 Weeks (plus or minues one week) ]
    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.

  2. Feasibility [ Time Frame: 4 Weeks (plus or minus one week) ]
    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



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Ages Eligible for Study:   1 Year to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 weight-for-length/height >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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01966731


Locations
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Angola
Hospital Pediátrico David Bernardino
Luanda, Angola
Congo, The Democratic Republic of the
Centre Hospitalier Monkole
Kinshasa, Congo, The Democratic Republic of the
Kenya
KEMRI/Wellcome Trust Research
Kilifi, Kenya
Uganda
Ministry of Health Mbale Regional Hospital
Mbale, Uganda
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Bristol-Myers Squibb
Investigators
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Principal Investigator: Russell Ware, MD, PhD Children's Hospital Medical Center, Cincinnati

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01966731     History of Changes
Other Study ID Numbers: 2013-4221
First Posted: October 22, 2013    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Africa

Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors