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

NCT01892644 | Withdrawn Phase 2

• 1 other identifier: 2012/2139
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemochromatosis; Myelodysplastic Syndromes

Keywords

Hemochromatosis; Myelodysplastic syndromes; Iron overload; Deferasirox; Chelation therapy; Venesection; Phlebotomy; Ferritin; Transfusional siderosis

Outcome Measures

Primary Outcomes (1)

• 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.

  0, 6 and 12 months

Secondary Outcomes (15)

• Change of hepcidin concentration in serum

  0, 6 and 12 months

• Change of non-transferrin bound iron (NTBI) concentration in serum

  0, 6 and 12 months

• Change of multiple trace metals in serum

  0, 6 and 12 months

• Change of intracellular signal molecules, mTOR, NFkB and stress sensor p53 in blood cells

  0, 6 and 12 months

• Change of 8-oxodG in urine

  0, 6 and 12 months

Other Outcomes (1)

• Pregnancy urin test (hCG)

  0, 6 and 12 months, 5 weeks posttreatment

Study Arms (4)

Deferasirox HC

ACTIVE COMPARATOR

10 patients with hemochromatosis treated with Deferasirox

Drug: Deferasirox

Venesection HC

ACTIVE COMPARATOR

10 patients with hemochromatosis treated with venesection

Other: Venesection

Deferasirox MDS

ACTIVE COMPARATOR

20 patients with myelodysplastic syndrome treated with Deferasirox

Drug: Deferasirox

Controls

NO INTERVENTION

10 healthy control persons to assess the normal level of investigational blood tests.

Interventions

Deferasirox DRUG

Deferasirox tablets ( 250 mg or 500 mg) dispersed in a drinkable solution, 10 mg/kg/day, once daily for 12 months

Also known as: Exjade

Deferasirox HC

Venesection OTHER

Treated with venesection every 8-10 day for 12 months, or until serum-ferritin has been reduced to about 50 µg/L.

Venesection HC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Previous or current venesection
• MDS patients eligible for hematopoietic stem cell transplantation
• 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)

Sponsors & Collaborators

• Haukeland University Hospital: lead
• Novartis: collaborator

Study Sites (1)

Haukeland University Hospital, Clinical Trial Unit

Bergen, 5021, Norway

Location

Related Publications (11)

• Brittenham GM. Iron-chelating therapy for transfusional iron overload. N Engl J Med. 2011 Jan 13;364(2):146-56. doi: 10.1056/NEJMct1004810.

  PMID: 21226580 BACKGROUND

• Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010 Aug;139(2):393-408, 408.e1-2. doi: 10.1053/j.gastro.2010.06.013. Epub 2010 Jun 11.

  PMID: 20542038 BACKGROUND

• Thorstensen K, Kvitland MA, Irgens WO, Hveem K, Asberg A. Screening for C282Y homozygosity in a Norwegian population (HUNT2): The sensitivity and specificity of transferrin saturation. Scand J Clin Lab Invest. 2010 Apr;70(2):92-7. doi: 10.3109/00365510903527838.

  PMID: 20073670 BACKGROUND

• Tziomalos K, Perifanis V. Liver iron content determination by magnetic resonance imaging. World J Gastroenterol. 2010 Apr 7;16(13):1587-97. doi: 10.3748/wjg.v16.i13.1587.

  PMID: 20355237 BACKGROUND

• Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.

  PMID: 9058730 BACKGROUND

• Brissot P, Ropert M, Le Lan C, Loreal O. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta. 2012 Mar;1820(3):403-10. doi: 10.1016/j.bbagen.2011.07.014. Epub 2011 Aug 9.

  PMID: 21855608 BACKGROUND

• Hori A, Mizoue T, Kasai H, Kawai K, Matsushita Y, Nanri A, Sato M, Ohta M. Body iron store as a predictor of oxidative DNA damage in healthy men and women. Cancer Sci. 2010 Feb;101(2):517-22. doi: 10.1111/j.1349-7006.2009.01394.x. Epub 2009 Oct 10.

  PMID: 19895603 BACKGROUND

• Barany E, Bergdahl IA, Bratteby LE, Lundh T, Samuelson G, Skerfving S, Oskarsson A. Iron status influences trace element levels in human blood and serum. Environ Res. 2005 Jun;98(2):215-23. doi: 10.1016/j.envres.2004.09.010.

  PMID: 15820728 BACKGROUND

• Phatak P, Brissot P, Wurster M, Adams PC, Bonkovsky HL, Gross J, Malfertheiner P, McLaren GD, Niederau C, Piperno A, Powell LW, Russo MW, Stoelzel U, Stremmel W, Griffel L, Lynch N, Zhang Y, Pietrangelo A. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology. 2010 Nov;52(5):1671-779. doi: 10.1002/hep.23879.

  PMID: 20814896 BACKGROUND

• Brissot P, Ball S, Rofail D, Cannon H, Jin VW. Hereditary hemochromatosis: patient experiences of the disease and phlebotomy treatment. Transfusion. 2011 Jun;51(6):1331-8. doi: 10.1111/j.1537-2995.2010.02997.x. Epub 2010 Dec 22.

  PMID: 21175649 BACKGROUND

• Messa E, Carturan S, Maffe C, Pautasso M, Bracco E, Roetto A, Messa F, Arruga F, Defilippi I, Rosso V, Zanone C, Rotolo A, Greco E, Pellegrino RM, Alberti D, Saglio G, Cilloni D. Deferasirox is a powerful NF-kappaB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging. Haematologica. 2010 Aug;95(8):1308-16. doi: 10.3324/haematol.2009.016824. Epub 2010 Jun 9.

  PMID: 20534700 BACKGROUND

MeSH Terms

Conditions

Hemochromatosis; Myelodysplastic Syndromes; Iron Overload

Interventions

Deferasirox; Phlebotomy

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rune J Ulvik, MD, PhD

  Dept. of Clinical Science and Lab. of Clinical Biochemistry, Univ. of Bergen and Haukeland University Hospital, Bergen, N5021, Norway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2013
• First Posted: July 4, 2013
• Study Start: May 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: April 3, 2024

Record last verified: 2024-04

Locations

NO (1)