Clinical trial NCT01254227: Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload
Official title: Phase II, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Patients With Severe Cardiac Iron Overload Due to Chronic Blood Transfusion (HYPERION)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Iron Overload
Keywords: Cardiac iron overload,
deferasirox,
deferoxamine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-12-06
Enrollment: 60
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: This study will evaluate the efficacy and safety of deferasirox in combination with deferoxamine followed be deferasirox monotherapy in patients with severe iron overload due to chronic blood transfusions.


Eligibility criteria: Inclusion Criteria:

* Patients with β-thalassemia major or Diamond-Blackfan anemia (DBA) or congenital sideroblastic anemia on chronic transfusion therapy
* Myocardial T2\* value that is ≥ 5 and \< 10 ms
* Left ventricular ejection fraction (LVEF) ≥ 56% as determined by Magnetic resonance imaging (MRI)
* Liver Iron Concentration (LIC) ≥ 7 mg Fe /g dw as determined by R2 MRI.
* Lifetime history of at least 50 units of red blood cell transfusions, and must be receiving at least ≥ 8 units/yr of red blood cell transfusions
* Serum ferritin ≥ 1000 ng/mL

Exclusion Criteria:

* Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias)
* Patients unable to undergo study assessments including MRI
* Patients with serum creatinine greater than Upper limit of normal ULN)range or with significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥1.0 mg/mg in a non-first void urine sample at baseline.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Change in Cardiac Iron Content From Baseline to Month 12
timeFrame: From Baseline to Month 12
Secondary outcomes:
measure: Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24
timeFrame: From the Months 6, 12, 18 and 24
measure: Change in Cardiac Iron Content From Baseline to Month 6,18 and 24
timeFrame: From Baseline to Months 6, 18 and 24
measure: Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24
timeFrame: From the Months 6, 12, 18 and 24
measure: Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24
timeFrame: From the Months 6, 12, 18 and 24
measure: Time to Achieve From Baseline (FAS) of at Least 10% at Month 24
timeFrame: At 24 months
measure: Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24
timeFrame: From the Baseline, Month 6, 12, 18 and Month 24
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Patra - RIO
country: Greece
facility: Novartis Investigative Site
state: GR
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Napoli
country: Italy
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: Antalya
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
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: Aydinok Y, Kattamis A, Cappellini MD, El-Beshlawy A, Origa R, Elalfy M, Kilinc Y, Perrotta S, Karakas Z, Viprakasit V, Habr D, Constantinovici N, Shen J, Porter JB; HYPERION Investigators. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload. Blood. 2015 Jun 18;125(25):3868-77. doi: 10.1182/blood-2014-07-586677. Epub 2015 May 1.