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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Haukeland University Hospital
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT01892644
First received: July 1, 2013
Last updated: NA
Last verified: July 2013
History: No changes posted
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change of hepcidin concentration in serum [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Change of non-transferrin bound iron (NTBI) concentration in serum [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Change of multiple trace metals in serum [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Change of intracellular signal molecules, mTOR, NFkB and stress sensor p53 in blood cells [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Change of 8-oxodG in urine [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    Marker of oxidative DNA damage

  • Change of Cu,Zn-SOD activity in erythrocyte hemolysate [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • HbA1c [ Time Frame: 0, 2,6,12 months ] [ Designated as safety issue: Yes ]
  • INR ( International normalized ratio) [ Time Frame: 0,2,6,12 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Urine trace metals [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Bone marrow sample [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]

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

Estimated Enrollment: 50
Study Start Date: May 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (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
Genders Eligible for Study:   Both
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

Contacts
Contact: Rune J Ulvik, MD, PhD +475597500 rune.ulvik@helse-bergen.no
Contact: Bjørn Tore Gjertsen, MD, PhD +475597500 bjorn.gjertsen@helse-bergen.no

Locations
Norway
Haukeland University Hospital, Clinical Trial Unit Recruiting
Bergen, Norway, 5021
Principal Investigator: Rune J Ulvik, MD, PhD         
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: July 1, 2013
Health Authority: Norway: Regional Ethics Commitee
Norway: Norwegian Medicines Agency

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

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

ClinicalTrials.gov processed this record on November 19, 2014