Pilot Pharmacokinetic Study In Patients With Inadequate Response To Deferasirox (Exjade)

The purpose of this trial is to examine three potential mechanisms of inadequate response to Exjade® in patients with transfusion dependent iron overload including patients with thalassemia syndromes, sickle cell disease and bone marrow failure.

Hypothesis: Patients have physiologic barriers to adequately respond to deferasirox that may include absorption, pharmacokinetics of drug metabolism, hepatic clearance and/or genetic factors.

Study objectives Primary objective

• To evaluate three potential mechanisms for inadequate response to deferasirox in a small cohort of patients with hemoglobinopathies.
• Oral pharmacokinetics measured with Cmax and AUC following standard dose deferasirox.
• Hepatobiliary excretory function
• Accessibility of chelatable iron pool by deferoxamine challenge Secondary objective(s)
• To identify risk factors that can predict adequate response including demographics, disease status, presence and severity of liver disease, trough levels of deferasirox at outpatient visits and pharmacogenomics.
• To investigate usefulness of potential surrogate measures of response including serum deferasirox levels, Hepatobiliary Iminodiacetic Acid (HIDA)nuclear medicine scan to evaluate hepatic excretory function and urinary iron excretion by deferoxamine challenge.

This is an investigator-initiated, pilot-scale, open-label physiological assessment of patients who respond poorly to deferasirox compared with patients who respond well. We plan to study 2 groups of patients: a)10 patients who have demonstrated poor responses and b) 5 control patients with good responses as defined further in the protocol. The study has two parts.