Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome

Launched by HAUKELAND UNIVERSITY HOSPITAL · Jul 1, 2013

Keywords

ClinConnect Summary

The two most important causes of iron overload disease in humans are the iron-loading disorder hereditary hemochromatosis (HC), and transfusional siderosis in patients with chronic hematological diseases like myelodysplastic syndrome (MDS), thalassemia, and leukemia.

Hemochromatosis. In HC the molecular regulation of iron uptake across the intestinal mucosa is disturbed, leading to hyperabsorption and accumulation of iron in parenchymal tissues such as the liver, pancreas, endocrine organs and heart. Hepcidin, a small peptide hormone synthesized in the liver, apparently functions as the ma...

Gender

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Eligibility criteria

• Inclusion Criteria:
• • Patients with hemochromatosis, aged \> 30 years, C282Y- homozygote, with serum-ferritin =/\> 1000 µg/L
• • Patients aged \> 18 years with verified low-risk or intermediate-1 risk of myelodysplastic syndrome, with normal cytogenetics and serum-ferritin \> 1500 µg/L, or with a transfusion history of =/\> red- blood-cell-transfusions.
• Exclusion Criteria:
• • Previous or current venesection
• • MDS patients eligible for hematopoietic stem cell transplantation
• • Subject complies with one or more of the following standard exclusion criteria for MRI examination;
• • If the patient has a pacemaker.
• • If the patient has a neurostimulator
• • If the patient has a "aneurismeclips"
• • If the patient has a foreign object in the eye. If yes, what object.
• • If the patient has a cochlea-/earimplant.
• • If the patient has a V/P shunt.
• • If the patient is claustrophobic.
• • If the patient has an artificial heart valve.
• • If the patient has known renal failure, eGFR \<30.
• • If the patient has or will have a liver transplantation.
• • Other: metal prostheses, metal implant
• • Presence of inflammation (CRP ≥ 5 mg/L)
• • Presence of proteinuria or creatinine \> 2 x UNL (Upper Normal Limit)
• • Estimated glomerular filtration rate (GFR) \< 60 mL/min
• • ALAT, ASAT, GT or ALP \> 2 x ULN ( Upper Normal Limit)
• • ALAT \> 90 U/L for women, ALAT \> 140 U/L for men
• • ASAT \> 70 U/L for women, ASAT \> 90 U/L for men
• • ALP \> 210 U/L for women and men
• • GT \> 90 U/L for women ≤ 40 years, GT \> 150 U/L for women \> 40 years
• • GT \> 160 U/L for men ≤ 40 years, GT \> 230 U/L for men \> 40 years
• • Acute or chronic hepatitis
• • Patients with chronic liver disease Child Pugh Class B and C
• • Chronic skin disease with rash
• • Estimated survival \< 6 months
• • Prior or concomitant treatment with other iron chelator therapies within 6 weeks of screening
• • History of non-compliance to medical regimens, or considered potentially unreliable and/or not cooperative
• • Uncontrolled diabetes, defined as glycolated hemoglobin (HbAlc) \> 8.5%
• • Presence of cataracts or hearing loss disease
• • Presence of a surgical or medical condition which might significantly alter absorption, distribution, metabolism or excretion of study drug
• • Planned in-hospital surgeries during the course of the study
• • Subjects who are pregnant, breast-feeding, or intending to become pregnant
• • Hypersensitivity to the active substance or the excipients in drug product
• • Any other reason why, in the opinion of the investigator, the patient should not participate (e.g. serious heart disease, infection, cancer, etc).