Effect of Deferiprone on Oxidative-Stress and Iron-Overload in Low Risk Transfusion-Dependent MDS Patients

Summary

The effect oral iron chelator Deferiprone on the Oxidative stress and on Iron Overload status in transfusion dependent, iron-overloaded low risk MDS patients; Primary Objective: • To evaluate the effect of Deferiprone on oxidative stress parameter - Reactive oxygen species (ROS). Secondary Objectives: * To evaluate the effect of Deferiprone on other oxidative stress parameters 1. Reduced glutathione 2. Membrane lipid peroxidation 3. External phosphatidylserine * To evaluate the change from baseline to last visit in parameters of iron load. 1. Serum ferritin (despite ongoing RBC transfusions during the study period). 2. LIP 3. LPI 4. serum hepcidin * To evaluate the change from one month preceding baseline visit to last month on study in transfusion requirements. * To monitor safety measures: 1. Adverse events (AEs). 2. Number of discontinuations due to AEs Study design: Single-arm, open-label, multi-center study in 20 iron-overloaded patients with low risk MDS. All participants will be treated with deferiprone for up to 4 months. Patients will have complete blood count monitored weekly, and will visit the site monthly for assessments of safety and efficacy.

Timeline

Start

2016-02

Primary completion

2017-05

Completion

2018-06

Publications

• Background Greenberg PL, Young NS, Gattermann N. Myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program. 2002:136-61. doi: 10.1182/asheducation-2002.1.136.
• Background Hellstrom-Lindberg E. Management of anemia associated with myelodysplastic syndrome. Semin Hematol. 2005 Apr;42(2 Suppl 1):S10-3. doi: 10.1053/j.seminhematol.2005.01.002. No abstract available.
• Background Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci. 1998 Jun 30;850:191-201. doi: 10.1111/j.1749-6632.1998.tb10475.x.
• Background Farquhar MJ, Bowen DT. Oxidative stress and the myelodysplastic syndromes. Int J Hematol. 2003 May;77(4):342-50. doi: 10.1007/BF02982641.
• Background Choi SO, Cho YS, Kim HL, Park JW. ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPalpha and STAT-3. Biochem Biophys Res Commun. 2007 Apr 27;356(1):312-7. doi: 10.1016/j.bbrc.2007.02.137. Epub 2007 Mar 5.
• Results Gattermann N, Rachmilewitz EA. Iron overload in MDS-pathophysiology, diagnosis, and complications. Ann Hematol. 2011 Jan;90(1):1-10. doi: 10.1007/s00277-010-1091-1. Epub 2010 Oct 12.
• Results Ghoti H, Amer J, Winder A, Rachmilewitz E, Fibach E. Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome. Eur J Haematol. 2007 Dec;79(6):463-7. doi: 10.1111/j.1600-0609.2007.00972.x. Epub 2007 Nov 1.
• Results Smeets ME, Vreugdenhil G, Holdrinet RS. Improvement of erythropoiesis during treatment with deferiprone in a patient with myelofibrosis and transfusional hemosiderosis. Am J Hematol. 1996 Mar;51(3):243-4. doi: 10.1002/(SICI)1096-8652(199603)51:33.0.CO;2-H. No abstract available.
• Results Cermak J. Erythropoietin administration may potentiate mobilization of storage iron in patients on oral iron chelation therapy. Hemoglobin. 2006;30(1):105-12. doi: 10.1080/03630260500455375.
• Results Payne KA, Rofail D, Baladi JF, Viala M, Abetz L, Desrosiers MP, Lordan N, Ishak K, Proskorovsky I. Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload. Adv Ther. 2008 Aug;25(8):725-42. doi: 10.1007/s12325-008-0085-z.
• Results Cermak J, Jonasova A, Vondrakova J, Walterova L, Hochova I, Siskova M, Neuwirtova R. Efficacy and safety of administration of oral iron chelator deferiprone in patients with early myelodysplastic syndrome. Hemoglobin. 2011;35(3):217-27. doi: 10.3109/03630269.2011.578515.
• Results Cermak J, Jonasova A, Vondrakova J, Cervinek L, Belohlavkova P, Neuwirtova R. A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes. Leuk Res. 2013 Dec;37(12):1612-5. doi: 10.1016/j.leukres.2013.07.021. Epub 2013 Aug 9.
• Results Kersten MJ, Lange R, Smeets ME, Vreugdenhil G, Roozendaal KJ, Lameijer W, Goudsmit R. Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann Hematol. 1996 Nov;73(5):247-52. doi: 10.1007/s002770050236.
• Results Telfer PT, Prestcott E, Holden S, Walker M, Hoffbrand AV, Wonke B. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol. 2000 Sep;110(4):971-7. doi: 10.1046/j.1365-2141.2000.02298.x.
• Results Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994 Sep 1;331(9):574-8. doi: 10.1056/NEJM199409013310903.

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