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

This study has been terminated.
(Failure to recruit patients with hemochromatosis to the Deferasirox arm)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT01892644
First received: July 1, 2013
Last updated: January 20, 2017
Last verified: January 2017
  Purpose

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.


Condition Intervention Phase
Hemochromatosis Myelodysplastic Syndromes Drug: Deferasirox Other: Venesection Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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.

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • Pregnancy urin test (hCG) [ Time Frame: 0, 6 and 12 months, 5 weeks posttreatment ]

Enrollment: 50
Study Start Date: May 2013
Study Completion Date: January 2017
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Deferasirox HC
10 patients with hemochromatosis treated with Deferasirox
Drug: 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
Other: 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
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01892644

Locations
Norway
Haukeland University Hospital, Clinical Trial Unit
Bergen, Norway, 5021
Sponsors and Collaborators
Haukeland University Hospital
Novartis
Investigators
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
  More Information

Publications:

Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT01892644     History of Changes
Other Study ID Numbers: 2012/2139
Study First Received: July 1, 2013
Last Updated: January 20, 2017

Keywords provided by Haukeland University Hospital:
Hemochromatosis
Myelodysplastic syndromes
Iron overload
Deferasirox
Chelation therapy
Venesection
Phlebotomy
Ferritin
Transfusional siderosis

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Iron Overload
Hemochromatosis
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Iron Metabolism Disorders
Metabolic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 23, 2017