Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study (THALASSA)
Non-transfusion Dependent Thalassemia
About this trial
This is an interventional treatment trial for Non-transfusion Dependent Thalassemia focused on measuring Thalassemia, thalassemia intermedia, alpha-thalassemia, beta-thalassemia, deferasirox, iron overload, non-transfusion dependent
Eligibility Criteria
Core Inclusion Criteria:
- Male or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old
- Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
- Serum ferritin >300 ng/mL at screening
Core Exclusion Criteria:
- Hemoglobin S (HbS)-variants of thalassemia syndromes
- Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) throughout the study course will not be excluded
- Any blood transfusion 6 months prior to study start
- Creatinine clearance ≤ 60 mL/min at screening
- Serum creatinine above the upper limit of normal at both screening visits
- Significant proteinuria as indicated by a urine protein/urine creatinine ratio > 1.0 mg/mg
- Alanine aminotransferase (ALT) of > 5 x the upper limit of normal at both screening visits
- Concomitant therapy with hydroxyurea, erythropoietin, butyrate
- History of deferasirox treatment
- Pediatric patients: a patient's weight of below 20 kg
Extension Inclusion Criteria:
- Patients who completed the core CICL670A2209 clinical trial
- Written informed consent obtained prior entry to one year extension study CICL670A2209
Extension Exclusion Criteria:
- Patients with a continuous increase in serum creatinine ≥ 33% above the baseline value and > ULN who did not improve after drug interruption or dose reduction in the core study
- Patients with a continuous increase in ALT greater than 2 times the baseline value and > 5 times ULN who did not improve after drug interruption or dose reduction in the core study
- Patients with progressive proteinuria, as assessed by the investigator, who did not improve after drug interruption or dose reduction in the core study
- Significant medical condition interfering with the ability to partake in this study (e.g.systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.)
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Children's Hospital & Research Center Oakland
- Children's Memorial Hospital/Division of Hematology/Oncology
- New York Presbyterian Hospital/Weill Medical College of Cornell University
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Placebo Comparator
Placebo Comparator
5 mg/kg/day deferasirox
10 mg/kg/day deferasirox
5 mg/kg/day placebo
10 mg/kg/day placebo
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
Placebo tablet matching 5 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
Placebo tablet matching 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.