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) - HYPERIO

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 45

Inclusion Criteria

• Age = 10 years
• Male or female patients with ß-thalassemia major or DBA or congenital sideroblastic anemia on chronic transfusion therapy
• Myocardial T2* value that is = 5 and < 10 ms
• LVEF = 56 % as determined by MRI
• 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
• Written informed consent obtained prior to any screening procedures
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

• 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 MRI 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) = 1.0 mg/mg in a non-first void urine sample at baseline
• Patients with ALT (SGPT) levels >5 x ULN only if their LIC is <10 mg Fe/g dw
• 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)
• Significant medical condition interfering with the ability to partake in this study (e.g.uncontrolled hypertension, systemic cardiovascular, renal, hepatic disease, etc.)
• Patients with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption
• History of hypersensitivity to any of the study drugs or their excipients
• 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 or cervical carcinoma in situ
• 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 and receiving an investigational drug
• Patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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