Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome (DefeHEMY)
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.
|Hemochromatosis Myelodysplastic Syndromes||Drug: Deferasirox Other: Venesection||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Deferasirox Versus Venesection in Patients With Hemochromatosis and for Treatment of Transfusional Siderosis in Myelodysplastic Syndrome: Diagnostics and New Biomarkers.|
- Changes from baseline in liver iron concentration (LIC) and heart iron concentration (HIC) determined by Magnetic Resonance Imaging (MRI), and in bone marrow iron content determined by microscopy after treatment with deferasirox. [ Time Frame: 0, 6 and 12 months ]
- Change of hepcidin concentration in serum [ Time Frame: 0, 6 and 12 months ]
- Change of non-transferrin bound iron (NTBI) concentration in serum [ Time Frame: 0, 6 and 12 months ]
- Change of multiple trace metals in serum [ Time Frame: 0, 6 and 12 months ]
- Change of intracellular signal molecules, mTOR, NFkB and stress sensor p53 in blood cells [ Time Frame: 0, 6 and 12 months ]
- Change of 8-oxodG in urine [ Time Frame: 0, 6 and 12 months ]Marker of oxidative DNA damage
- Change of Cu,Zn-SOD activity in erythrocyte hemolysate [ Time Frame: 0, 6 and 12 months ]Cu,Zn-Super Oxid Dismutase (SOD)is an antioxidant enzyme
- Clinical chemistry: Na, K, Ca, Creatinine, creatinine kinase, CRP, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), lactate dehydrogenase (LD), albumin, bilirubin. [ Time Frame: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment ]Serum analysis
- Urine routine test strip for detection of blood, protein, and nitrite [ Time Frame: 0,2,4,6,8 weeks and 3,4,5,6,7,8,9,10,11,12 months ]Morning spot urine sample.
- Ferritin concentration in serum [ Time Frame: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment ]
- Transferrin saturation in serum [ Time Frame: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment ]
- HbA1c [ Time Frame: 0, 2,6,12 months ]
- INR ( International normalized ratio) [ Time Frame: 0,2,6,12 months ]
- Analysis of hemoglobin, reticulocytes, hematocrit, MCV, leukocyte count (total and differential), and platelets [ Time Frame: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment ]
- Urine trace metals [ Time Frame: 0, 6 and 12 months ]
- Bone marrow sample [ Time Frame: 0, 6 and 12 months ]
- Pregnancy urin test (hCG) [ Time Frame: 0, 6 and 12 months, 5 weeks posttreatment ]
|Study Start Date:||May 2013|
|Study Completion Date:||January 2017|
|Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Deferasirox HC
10 patients with hemochromatosis treated with Deferasirox
Deferasirox tablets ( 250 mg or 500 mg) dispersed in a drinkable solution, 10 mg/kg/day, once daily for 12 months
Other Name: Exjade
Active Comparator: Venesection HC
10 patients with hemochromatosis treated with venesection
Treated with venesection every 8-10 day for 12 months, or until serum-ferritin has been reduced to about 50 µg/L.
Active Comparator: Deferasirox MDS
20 patients with myelodysplastic syndrome treated with Deferasirox
Deferasirox tablets ( 250 mg or 500 mg) dispersed in a drinkable solution starting with 10 mg/kg/day, once daily for 2 weeks and thereafter 20 mg/kg/day for 11,5 months.
Other Name: Exjade
No Intervention: Controls
10 healthy control persons to assess the normal level of investigational blood tests.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01892644
|Haukeland University Hospital, Clinical Trial Unit|
|Bergen, Norway, 5021|
|Principal Investigator:||Rune J Ulvik, MD, PhD||Dept. of Clinical Science and Lab. of Clinical Biochemistry, Univ. of Bergen and Haukeland University Hospital, Bergen, N5021, Norway|