Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies
Condition: Sickle Cell Anemia
MeSH terms: Anemia, Sickle Cell
Intervention: Hydroxyurea
Intervention description: Given orally once daily.
Intervention MeSH terms: Hydroxyurea
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 58.0
Sex: All
Minimum age: 9 Months
Maximum age: 36 Months
Healthy volunteers: No
Keywords: Sickle cell; Hydroxyurea; Infants

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Children with HbSS or sickle hemoglobin (HbS)/β^0thalassemia

          -  ≥9 to ≤ 36 months of age at study initiation

          -  Enrollment will occur irrespective of clinical severity

        Exclusion Criteria:

        Permanent:

          -  Receiving chronic red blood cell transfusion therapy.

          -  Condition or chronic illness, which in the opinion of the PI makes participation
             unsafe.

        Transient (participants may be re-evaluated after ≥14 days):

          -  Recent (<30 days) participation in another clinical intervention trial utilizing an
             investigational new drug/investigational device exemption (IND/IDE) agent.

          -  Erythrocyte transfusion in the past 2 months.

          -  Laboratory Assessments:

               -  Hemoglobin <6.0 g/dL

               -  Absolute reticulocyte count <80 * 10^3/µL if hemoglobin <9.0 mg/dL

               -  Absolute neutrophil count <1.5 * 10^3/µL

               -  Platelet count <100 * 10^3/µL

               -  Serum creatinine > twice the upper limit of normal for age

               -  Alanine aminotransferase (ALT) > twice the upper limit of normal