Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate changes in cardiac iron as measured by MRI T2* in beta-thalassemia patients with deferasirox treatment.

Official Title
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An Open Label Trial Evaluating Cardiac T2* in Beta-thalassemia Patients on Deferasirox (ICL670) Treatment for 18 Months

Conditions
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Beta-thalassemia, Iron Overload

Intervention / Treatment
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* Drug: Deferasirox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female β-thalassemia outpatients on chronic transfusion therapy (defined as > 8 transfusions per year) Lifetime minimum of 100 previous packed red blood cell transfusions Patients currently on chelation therapy will require a one day wash out prior to the first dose of study drug Age ≥ 10 years Sexually active females of childbearing potential must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy. Exclusion Criteria: Ejection Fraction < 56 % measured using steady-state free precession imaging by MRI Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, intrauterine device or any other MRI incompatible metal implants or intractable claustrophobia Abnormal laboratory values as defined by the protocol Clinical or laboratory evidence of active Hepatitis B or Hepatitis C History of HIV positive test result (ELISA or Western blot) Uncontrolled systemic hypertension Second or third degree A-V block Life-threatening arrhythmias, including sustained ventricular tachycardia and aborted sudden death, within the last year History of cardiac conditions or unstable cardiac disease not controlled by standard medical therapy History of clinically relevant ocular toxicity related to iron chelation Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment Pregnancy or breast feeding (documented negative pregnancy test required for study entry) Patients enrolled in an ongoing clinical trial of deferasirox (ICL670) cannot be withdrawn in order to participate in this study Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative Other inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: deferasirox every day for 77 weeks<br>Participants received Deferasirox 30 milligrams per kilogram per day (mg/kg/day) orally once daily (OD), 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 gram (g), tablets were dissolved in at least 100 milliliter (mL) of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed. | Drug: Deferasirox<br>* Oral deferasirox 30mg/kg/day once per day for 77 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2* | Cardiac T2* was measured in the short axis plane at the widest point of a 4-chamber localizer using custom breath-hold R2* gradient echo sequences modeled after techniques used by Anderson et al (2001) and Westwood et al (2003). | From Baseline to 25, 49, 77 Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks | MRI evaluation of liver iron concentration has been validated by liver biopsy (St Pierre et al 2005). Studies comparing T2* values of liver iron concentration (LIC) with LIC as assessed by biopsy have confirmed that T2* values reflect liver iron content (Wood et al 2003b). Direct tissue-validation of cardiac T2* measurements in humans has not been performed because endomyocardial biopsy is a dangerous and unreliable indicator of cardiac iron overload (Olson et al 1989, Fitchett et al 1980). However, it has been shown that cardiac T2* accurately reflects cardiac iron in a gerbil iron cardiomyopathy model (Wood et al 2004b). T2* measurements have shown excellent inter-scanner and inter-exam reproducibility, making them suitable for longitudinal monitoring (Westwood et al 2003a, Westwood et al 2003b). | From Baseline to 25, 49, 77 Week | 
| Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks | Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader. | From Baseline to 25, 49, 77 Week | 
| Serum Ferritin and Changes From Baseline in Serum Ferritin During Study | Serum ferritin will be assessed at each study visit. Analysis was performed in Completer population consists of those participants who had a Week 77 MRI. | From Baseline to 25, 49, 77 Week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron Chelation, Deferasirox, Chelator, Desferal, beta-thalassemia, Iron overload