Hydroxyurea Management in Kids: Intensive Versus Stable Dosage Strategies

Status:	Recruiting
Conditions:	Anemia
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	Any
Updated:	9/20/2018
Start Date:	May 12, 2017
End Date:	September 30, 2020
Contact:	Jeremie Estepp, MD
Email:	referralinfo@stjude.org
Phone:	866-278-5833

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.

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.

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 g/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

We found this trial at

sites

University of Mississippi Medical Center

2500 N State St
Jackson, Mississippi 39216

(601) 984-1000