Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies

• Status: Completed
• Trial end date: 2020-06-08
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Hydroxyurea

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