Beta-thalassemia major (TM) or Diamond Blackfan anemia (DBA) or myelodysplastic syndromes (MDS) (low and INT-1 risk as per the IPSS for MDS) or sideroblastic anemia and myocardial iron overload as indicated by a T2* =6 but not greater than 20 ms, with no symptoms of cardiac dysfunction, and an MRI measured LVEF =56%.
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age =10 years. • Male or female patients with ß-thalassemia major or DBA or myelodysplsatic syndromes (MDS) (low and INT-1 risk as per the IPSS for MDS) or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study. • Myocardial T2* value that is = 6 but not >20 ms. Patients enrolled with a baseline T2* less than 10 ms will undergo additional CMR assessments, every 3 months, to evaluate cardiac function and cardiac iron as part of safety monitoring. • 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. • LVEF = 56 % as determined by CMR. • LIC = 3 mg Fe / g dw, as determined by R2 MRI. • Only patients chelated or who need any chelation therapy. Chelated patients will undergo a 5-day washout period prior to commencing 12 month study treatment. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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, who: • Are claustrophobic to MRI. • Have a pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (e.g., some types of aneurysm clips, shrapnel in proximity to vital organs such as the retina). • Are obese (exceeding the equipment limits). • Patients with serum creatinine > ULN or with significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) =1.0mg/mg in a non-first void urine sample at baseline. If serum creatinine is found to be >ULN or UPCR is found to be =1mg/mg the test can be repeated after 1 month. • Patients with ALT (SGPT) levels > 5 x ULN only if their LIC is 5 x ULN and LIC <10mg Fe/g dw the test can be repeated after 1 month. • Patients with considerable impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox / ICL670 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). • History of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy. • Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol. • Patients with a known history of HIV seropositivity (Elisa or Western blot). • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. • Pregnant, nursing or at risk of becoming pregnant • Participating in another clinical trial or receiving an investigational drug. • History of non-compliance with medical regimens or considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol • Patients with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption • History of hypersensitivity to any of the study drugs or their excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effects of deferasirox and deferoxamine treatment on myocardial iron content, as depicted by changes in T2* MRI over a period of 12 months.; Secondary Objective: • To compare treatment with deferasirox vs. deferoxamine as determined by change in: CMR measured LVEF after 12 months treatment (key secondary objective); CMR measured LVEF after 6 months treatment; myocardial T2* after 6 months treatment; CMR measured left ventricular end systolic and diastolic volume indices (LVESVI and LVEDVI) and left ventricular mass indices (LVMI) after 6 and 12 months treatment. • Proportion of patients dropping out of study due to cardiac dysfunction. • To compare the safety and tolerability of deferasirox vs. deferoxamine in this patient population. • To determine the single and repeated-dose deferasirox pharmacokinetics through parameters over the 12 months of treatment and to construct a PK profile for the 40 mg/kg/day deferasirox dose. • To collect additional data on safety and efficacy of deferasirox and deferoxamine in patients with cardiac iron deposition when treated for up to 12 months in the extension study (Post-text supplement 6). ;Primary end point(s): Ratio of myocardial T2* after 12 months treatment with deferasirox vs deferoxamine divided by that at screening (baseline). | — |
Countries
Italy, United Kingdom
Contacts
Public ContactMedical Collaboration Centre
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed