Clinical trial NCT00600938: Evaluating Use of Deferasirox as Compared to Deferoxamine in Treating Cardiac Iron Overload
Official title: A Multicenter, Randomized, Open-label Phase II Trial Evaluating Deferasirox Compared With Deferoxamine in Patients With Cardiac Iron Overload Due to Chronic Blood Transfusions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transfusional Iron Overload
Transfusional Hemosiderosis
Keywords: iron overload
cardiac iron
haemosiderosis
myocardial T2*
left ventricular ejection fraction
LVEF
cardiac dysfunction
thalassaemia
Diamond Blackfan anemia
DBA
sideroblastic anemia
myelodysplastic syndromes
MDS (low and INT-1 risk as per the IPSS for MDS)
liver MRI
deferasirox
deferoxamine
ICL670
DFO
cardiovascular magnetic resonance imaging
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-01-25
Enrollment: 197
Sex: ALL
Minimum age (years): 10
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a clinical research study in patients who have iron overload in the heart due to chronic blood transfusions.

The study will have 2 treatment groups and will compare the safety and efficacy of chelation therapy with a medicine called deferasirox (ICL670) with another medicine called deferoxamine (DFO). The study is aimed at finding out which of the two medicines is the best for treating iron overload in the heart.

Patients will be treated for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study treatment in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the heart and the liver will be evaluated using specific magnetic resonance imaging (MRI) assessments.


Eligibility criteria: Inclusion criteria:

* Male or female patients, aged 10 years and above, with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study.
* Patients with cardiac iron as measured by a myocardial T2\* value that is ≥ 6ms but not ≥ 20 ms.
* Patients with a lifetime history of at least 50 units of red cell transfusions, and must be receiving at least ≥10 units/yr of red blood cells transfusions.
* Patients with a left ventricular ejection fraction (LVEF) ≥ 56 % as determined by cardiovascular magnetic resonance (CMR).
* Patients with liver iron content (LIC) value ≥ 3 mg Fe / g dw, as determined by liver MRI.

Exclusion criteria:

* Patients with clinical symptoms of cardiac dysfunction.
* Patients unable to undergo study assessments including MRI
* Patients participating in another clinical trial or receiving an investigational drug.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment
timeFrame: 12 Month
Secondary outcomes:
measure: Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: 12 Month
measure: Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: 6 Month
measure: Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment
timeFrame: 6 Month
measure: Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
timeFrame: 6 Month, 12 Month
measure: Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
timeFrame: 6 Month, 12 Month
measure: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Mass Indices (LVMI)
timeFrame: 6 Month, 12 Month
measure: Core Study: Cardiac Function and the Proportion of Patients Dropping Out Due to Cardiac Dysfunction After Treatment With Deferasirox vs. Deferoxamine
timeFrame: 12 Month
measure: Core Study: Safety and Tolerability of Deferasirox vs Deferoxamine Over the 12 Months Treatment Period.
timeFrame: 12 Month
measure: Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Area Under the Plasma Concentration-time Curve for a Dosing Interval (AUCtau)
timeFrame: 12 Month
measure: Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Cmax)
timeFrame: 12 Month
measure: Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Time Points of Concentration Data
timeFrame: Month 1 and month 2 (pre-dose, 1,2 and 4 hours post-dose)
measure: Extension Study: Change From Baseline in Myocardial T2* After 24 Months Treatment
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Systolic Volume Indices (LVESVI)
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: Cardiac Function From Baseline to Month 24 by Change in Left Ventricular Mass Indices (LVMI)
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: The Cardiac Iron Concentration From T2* Values
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
timeFrame: Months 6, 12, 18 and 24
measure: Extension Study: Change in Serum Ferritin From Baseline by Month
timeFrame: Months 6, 12, 18 and 24
measure: Core Study: Single and Repeated Dose Pharmacokinetics of Deferasirox, Maximum Plasma Concentration (Tmax)
timeFrame: 12 Month
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Nanning
country: China
facility: Novartis Investigative Site
state: Guangxi
city: Limassol
country: Cyprus
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Mansoura
country: Egypt
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Hazmiyeh
country: Lebanon
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Antalya
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Dubai
country: United Arab Emirates
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Pennell DJ, Porter JB, Piga A, Lai YR, El-Beshlawy A, Elalfy M, Yesilipek A, Kilinc Y, Habr D, Musallam KM, Shen J, Aydinok Y; CORDELIA study investigators. Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine. Am J Hematol. 2015 Feb;90(2):91-6. doi: 10.1002/ajh.23876. Epub 2014 Nov 19.
citation: Pennell DJ, Porter JB, Piga A, Lai Y, El-Beshlawy A, Belhoul KM, Elalfy M, Yesilipek A, Kilinc Y, Lawniczek T, Habr D, Weisskopf M, Zhang Y, Aydinok Y; CORDELIA study investigators. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in beta-thalassemia major (CORDELIA). Blood. 2014 Mar 6;123(10):1447-54. doi: 10.1182/blood-2013-04-497842. Epub 2014 Jan 2.