Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies
Condition: Sickle Cell Anemia
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a pilot study, single-blind, randomized, multicenter, therapeutic clinical trial
      designed to evaluate the feasibility of enrolling infants and toddlers (9 months to 36
      months) with sickle cell anemia (SCA; HbSS or HbSβ^0thalassemia), regardless of disease
      severity, to a therapeutic trial. A prior clinical trial at St. Jude Children's Research
      Hospital (SJCRH) (BABYHUG, NCT01783990) demonstrated that a fixed dose (20 mg/kg/day) of
      hydroxyurea was safe and effective in decreasing SCA-related complications in very young
      children (9-18 months), and largely due to these findings, hydroxyurea is recommended to be
      offered to all children (≥9 months old) with SCA, independent of disease severity.
      Nevertheless, children in the treatment arm of BABYHUG continued to experience vaso-occlusive
      symptoms and to incur organ damage. In clinical trials of older children with SCA,
      intensification of hydroxyurea to a maximum tolerated dosage (MTD), defined by mild to
      moderate myelosuppression, may be associated with improved laboratory parameters compared to
      fixed lower-dosing, but the clinical benefits gained from dose intensification have not been
      described. Therefore, in this trial, children in the standard treatment arm will receive a
      fixed dose of hydroxyurea (20 mg/kg/day), and participants in the experimental arm will
      receive hydroxyurea intensified to MTD, defined by a goal absolute neutrophil count (ANC) of
      1500-3000 cells/µL. This trial aims to establish a multicenter infrastructure that will
      identify, enroll and randomize very young children (9-36 months) to receive fixed dose versus
      intensified-dose hydroxyurea in a single blinded manner, and to obtain prospective pilot data
      comparing the clinical and laboratory outcomes between the treatment arms to facilitate
      design of a definitive phase III trial.
    

Detailed description: 
      All participants will initially receive hydroxyurea at a dose of ~20 mg/kg/day in an open
      label fashion for eight weeks (± 2 weeks) prior to randomization. Participants will receive
      monthly medical evaluations (every 4 ± 2 weeks) where they will have height and weight
      measurements, medical history, physical examination, and medication adherence assessments.
      During these monthly visits complete blood counts with absolute reticulocyte count will be
      monitored. Hemoglobin electrophoresis, complete serum chemistries, urinalysis, lactate
      dehydrogenase and quality of life measurements will be obtained every 20 (±2) weeks.
      Transcranial Doppler (TCD) ultrasound velocities will be obtained at study entry (in
      participants ≥2 years of age) and study exit. Participants randomized to receive hydroxyurea
      at MTD will have their dose increased by 5 mg/kg/day every 8 weeks, in the absence of
      toxicity, until a goal ANC of 1500-3000 cells/µL is achieved, up to a maximum of 35
      mg/kg/day.

      Both groups will receive their assigned treatment for 48 weeks (± 3 weeks). Participants will
      be in the study for a total of 56 weeks (± 3 weeks) and have 14 clinic visits to the St. Jude
      outpatient Hematology Clinic during that time. After the 56 weeks, participants will be
      followed for an additional 30 days for side effects and will then be taken off study.
    

Intervention name(s): Hydroxyurea
Intervention type(s): Drug
Intervention description(s): Given orally once daily.
Other intervention name(s): HU
Intervention MeSH terms: Hydroxyurea
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Sickle cell; Hydroxyurea; Infants