Clinical trial NCT00447694: Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment
Official title: An Open Label Trial Evaluating Cardiac T2* in Beta-thalassemia Patients on Deferasirox (ICL670) Treatment for 18 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Beta-thalassemia
Iron Overload
Keywords: Iron Chelation
Deferasirox
Chelator
Desferal
beta-thalassemia
Iron overload
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-03-15
Enrollment: 30
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Magnetic Resonance Imaging (MRI) T2* and Absolute Change From Baseline in MRI T2*
timeFrame: From Baseline to 25, 49, 77 Week
Secondary outcomes:
measure: Change From Baseline in Liver Iron Concentration (LIC) Was Measured by MRI R2 From Absolute Change From Baseline to 101 Weeks
timeFrame: From Baseline to 25, 49, 77 Week
measure: Left Ventricular Ejection Fraction (LVEF) and Change in Left Ventricular Ejection Fraction From Baseline to 101 Weeks
timeFrame: From Baseline to 25, 49, 77 Week
measure: Serum Ferritin and Changes From Baseline in Serum Ferritin During Study
timeFrame: From Baseline to 25, 49, 77 Week
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
Study officials:
affiliation: Childresn's Hospital of Los Angeles
name: Thomas Coates, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Memorial Hospital of Chicago
name: Alexis Thompson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital and Research Center at Oakland
name: Paul Harmatz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wood JC, Glynos T, Thompson A, Giardina P, Harmatz P, Kang BP, Paley C, Coates TD. Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial. Haematologica. 2011 Jul;96(7):1055-8. doi: 10.3324/haematol.2010.032862. Epub 2011 Mar 10.
citation: Wood JC, Kang BP, Thompson A, Giardina P, Harmatz P, Glynos T, Paley C, Coates TD. The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood. 2010 Jul 29;116(4):537-43. doi: 10.1182/blood-2009-11-250308. Epub 2010 Apr 26.