Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload

Phase 2

Completed

Conditions: Cardiac Iron Overload

Interventions: Drug: Deferasirox and Deferoxamine

Registration Number: NCT01254227

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Deferasirox	Deferasirox and Deferoxamine	Deferoxamine combination followed by Deferasirox monotherapy

Primary Outcome Measures

Name	Time	Method
Change in Cardiac Iron Content From Baseline to Month 12	From Baseline to Month 12	Cardiac T2\* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2\* value of \<10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2\* or do not have any post-baseline T2\* are excluded from the analysis.

Secondary Outcome Measures

Name	Time	Method
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24	From the Baseline, Month 6, 12, 18 and Month 24	Cardiac iron concentration (mg Fe/g dw) was quantified using the formula (cardiac iron concentration (mg Fe/g dw) = 45 \* T2\* (ms) \^ (-1.22) and analyzed over time.
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24	From the Months 6, 12, 18 and 24	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.
Time to Achieve From Baseline (FAS) of at Least 10% at Month 24	At 24 months	Time from date of start of study treatment to date when first achieving T2\* ≥ 10 ms (but at least 10% relative increase from baseline) was summarized using the reverse Kaplan-Meier estimates (1 - Kaplan-Meier estimates) for the FAS.
Change in Cardiac Iron Content From Baseline to Month 6,18 and 24	From Baseline to Months 6, 18 and 24	The change in cardiac iron content was calculated as ratio of Cardiac T2\* at different time points; the efficacy endpoint analyses were performed on the Full Analysis Set (FAS).
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24	From the Months 6, 12, 18 and 24	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.
Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24	From the Months 6, 12, 18 and 24	The number of evaluable participants at each visit were used as the denominator for the calculation of proportion at each visit.