Novartis Exjade/Deferasirox Cardiac Iron A2206

Trial overview

A multicenter, randomized, open-label phase II trial evaluating deferasirox compared with deferoxamine in
patients with cardiac iron overload due to chronic blood transfusions

Inclusion criteria

• Age ≥10 years.
• Male or female patients with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study.
• Myocardial T2* value that is ≥ 10 but not >20 ms.
• 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 on chelation therapy with deferoxamine (DFO, Desferal®), deferasirox (ICL670, Exjade®) or deferiprone (L1, Ferriprox®) or a combination of DFO and L1 will be enrolled. Patients will undergo a 2-day washout period prior to commencing 12 month study treatment.

Exclusion criteria

• Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema).
• 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 ≥ 1.0 in a non-first void urine sample at baseline.
• Patients with ALT (SGPT) levels > 5 x ULN.
• 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 or nursing (lactating) women are not eligible to participate in the study. Females of reproductive potential must be willing during the entire study period to use one or more of the following acceptable methods of contraception, namely:
i) surgical sterilization (e.g., bilateral tubal ligation, vasectomy)
ii) hormonal contraception (implantable, patch, oral)
and iii) double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap).
• Patients participating in another clinical trial or receiving an investigational drug.
• History of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol.