Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies
Status:
Completed
Trial end date:
2020-06-08
Target enrollment:
Participant gender:
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.