Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with beta-thalassemia major.
OBJECTIVE
Deferasirox (ICL670) is a novel once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. This study evaluated the safety and tolerability of deferasirox in pediatric patients with transfusion-dependent beta-thalassemia major. Efficacy and pharmacokinetic assessments were secondary objectives.


METHODS
Forty patients equally stratified into two age groups--children (2 to <12 years) and adolescents (12-17 years)--were treated with deferasirox for 48 weeks. All received once-daily deferasirox 10 mg/kg/day with modifications allowed after 12 weeks' treatment. Safety, liver iron concentration (LIC), serum ferritin and pharmacokinetics were assessed.


RESULTS
Thirty-nine patients completed the study. One withdrew due to a skin rash. Adverse events were typical of this population, but only four were considered related to the study drug: mild nausea (two adolescents) and moderate skin rash (two children). There were no serious adverse events related to the study drug. Five patients briefly interrupted treatment due to elevated transaminases with no recurrences when treatment resumed. The mean deferasirox dose was 11.3 mg/kg/day. Overall LIC increased gradually from week 12 as mean daily iron intake was higher than excretion. Steady-state plasma levels of deferasirox and its iron complex, Fe-[deferasirox]2, were comparable between children and adolescents.


CONCLUSIONS
Deferasirox was well tolerated by this pediatric population. Toxicities known to be associated with other commercially available iron chelators were not observed. The dose employed was too low to induce a net negative iron balance in this regularly transfused population. Pharmacokinetic data support a once-daily dosing regimen based on body weight.
Galanello
Renzo
R
Ospedale Regionale Microcitemie, Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Via Jenner s/n, 09121 Cagliari, Italy. renzo.galanello@mcweb.unica.it
Piga
Antonio
A
Forni
Gian Luca
GL
Bertrand
Yves
Y
Foschini
Maria Loreta
ML
Bordone
Elena
E
Leoni
Giovanbattista
G
Lavagetto
Antonella
A
Zappu
Antonietta
A
Longo
Filomena
F
Maseruka
Henry
H
Hewson
Nicola
N
Sechaud
Romain
R
Belleli
Rossella
R
Alberti
Daniele
D
D000284:Administration, Oral; D000293:Adolescent; D001565:Benzoates / Q000008:administration & dosage* / Q000097:blood; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D014230:Triazoles / Q000008:administration & dosage* / Q000097:blood; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox