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

• Status: Terminated
• Trial end date: 2017-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC.

Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment.

Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Haukeland University Hospital
• Collaborator: Novartis
• Treatments: Deferasirox

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).