SIMIDIS: Azacitidine and Beta Erythropoietin Treatment in Patients With Myelodysplastic Syndrome

Summary

The primary objective is to evaluate the efficacy of the treatment in response rate terms. Otherwise this study wants to evaluate the safety of the treatment.

Timeline

Start

2009-02

Primary completion

2011-06

Completion

2011-06

Publications

• Background Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189-99.
• Background 2. Brunning RD, Head D, Bennett JM, Vardiman JW, Flandrin G, Harris NL et al. Myelodysplastic syndromes: introduction. En: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Tumours of haematopoietic and lymphoid tissues. Lyon, IARC Press, 2001; 63-67.
• Background San Miguel JF, Sanz GF, Vallespi T, del Canizo MC, Sanz MA. Myelodysplastic syndromes. Crit Rev Oncol Hematol. 1996 May;23(1):57-93. doi: 10.1016/1040-8428(96)00197-7. No abstract available.
• Background Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S, Irriguible D, San Miguel JF. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood. 1989 Jul;74(1):395-408.
• Background Aul C, Giagounidis A, Germing U. Epidemiological features of myelodysplastic syndromes: results from regional cancer surveys and hospital-based statistics. Int J Hematol. 2001 Jun;73(4):405-410. doi: 10.1007/BF02994001.
• Background Sanz GF, Sanz MA, Greenberg PL. Prognostic factors and scoring systems in myelodysplastic syndromes. Haematologica. 1998 Apr;83(4):358-68.
• 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.
• Background Alessandrino EP, Amadori S, Barosi G, Cazzola M, Grossi A, Liberato LN, Locatelli F, Marchetti M, Morra E, Rebulla P, Visani G, Tura S; Italian Society of Hematology. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica. 2002 Dec;87(12):1286-306.
• Background Bowen D, Culligan D, Jowitt S, Kelsey S, Mufti G, Oscier D, Parker J; UK MDS Guidelines Group. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol. 2003 Jan;120(2):187-200. doi: 10.1046/j.1365-2141.2003.03907.x. No abstract available.
• Background NCCN practice guidelines for the myelodysplastic syndromes. National Comprehensive Cancer Network. Oncology (Williston Park). 1998 Nov;12(11A):53-80. No abstract available.
• Background Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, Passamonti F, Arcaini L, Maffioli M, Bernasconi P, Lazzarino M, Cazzola M. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005 Oct 20;23(30):7594-603. doi: 10.1200/JCO.2005.01.7038. Epub 2005 Sep 26.
• Background Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Lowenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL; World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-4.
• Background Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.
• Background Parker JE, Mufti GJ. The myelodysplastic syndromes: a matter of life or death. Acta Haematol. 2004;111(1-2):78-99. doi: 10.1159/000074488.
• Background Tehranchi R, Fadeel B, Forsblom AM, Christensson B, Samuelsson J, Zhivotovsky B, Hellstrom-Lindberg E. Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Blood. 2003 Feb 1;101(3):1080-6. doi: 10.1182/blood-2002-06-1774. Epub 2002 Sep 5.
• Background Tehranchi R, Invernizzi R, Grandien A, Zhivotovsky B, Fadeel B, Forsblom AM, Travaglino E, Samuelsson J, Hast R, Nilsson L, Cazzola M, Wibom R, Hellstrom-Lindberg E. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Blood. 2005 Jul 1;106(1):247-53. doi: 10.1182/blood-2004-12-4649. Epub 2005 Mar 8.
• Background Tehranchi R, Fadeel B, Schmidt-Mende J, Forsblom AM, Emanuelsson E, Jadersten M, Christensson B, Hast R, Howe RB, Samuelsson J, Zhivotovsky B, Hellstrom-Lindberg E. Antiapoptotic role of growth factors in the myelodysplastic syndromes: concordance between in vitro and in vivo observations. Clin Cancer Res. 2005 Sep 1;11(17):6291-9. doi: 10.1158/1078-0432.CCR-04-1850.
• Background Hellstrom-Lindberg E. Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol. 1995 Jan;89(1):67-71. doi: 10.1111/j.1365-2141.1995.tb08909.x.
• Background Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I, Grimfors G, Hesse-Sundin E, Hjorth M, Kanter-Lewensohn L, Linder O, Luthman M, Lofvenberg E, Oberg G, Porwit-MacDonald A, Radlund A, Samuelsson J, Tangen JM, Winquist I, Wisloff F; Scandinavian MDS Group. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003 Mar;120(6):1037-46. doi: 10.1046/j.1365-2141.2003.04153.x.
• Background Remacha AF, Arrizabalaga B, Villegas A, Manteiga R, Calvo T, Julia A, Fernandez Fuertes I, Gonzalez FA, Font L, Junca J, del Arco A, Malcorra JJ, Equiza EP, de Mendiguren BP, Romero M. Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group. Haematologica. 1999 Dec;84(12):1058-64.
• Background Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005 Aug 1;106(3):803-11. doi: 10.1182/blood-2004-10-3872. Epub 2005 Apr 19.
• Background Rigolin GM, Castoldi G. The role of rHuEpo in low-risk myelodysplastic syndrome patients. Leuk Lymphoma. 2005 Jun;46(6):823-31. doi: 10.1080/10428190500080348.
• Background Casadevall N, Durieux P, Dubois S, Hemery F, Lepage E, Quarre MC, Damaj G, Giraudier S, Guerci A, Laurent G, Dombret H, Chomienne C, Ribrag V, Stamatoullas A, Marie JP, Vekhoff A, Maloisel F, Navarro R, Dreyfus F, Fenaux P. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004 Jul 15;104(2):321-7. doi: 10.1182/blood-2003-07-2252. Epub 2004 Mar 30.
• Background Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003 Nov 20;349(21):2042-54. doi: 10.1056/NEJMra023075. No abstract available.
• Background Galm O, Herman JG, Baylin SB. The fundamental role of epigenetics in hematopoietic malignancies. Blood Rev. 2006 Jan;20(1):1-13. doi: 10.1016/j.blre.2005.01.006. Epub 2005 Feb 23.
• Background Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002 May 15;20(10):2429-40. doi: 10.1200/JCO.2002.04.117.
• Background Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL, Larson RA; Cancer and Leukemia Group B. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006 Aug 20;24(24):3895-903. doi: 10.1200/JCO.2005.05.4346.
• Background Kornblith AB, Herndon JE 2nd, Silverman LR, Demakos EP, Odchimar-Reissig R, Holland JF, Powell BL, DeCastro C, Ellerton J, Larson RA, Schiffer CA, Holland JC. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002 May 15;20(10):2441-52. doi: 10.1200/JCO.2002.04.044.
• Background Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL, Leighton JK, Patel H, Rahman A, Sridhara R, Wang YC, Pazdur R; FDA. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res. 2005 May 15;11(10):3604-8. doi: 10.1158/1078-0432.CCR-04-2135.
• Background Cazzola M, Malcovati L. Myelodysplastic syndromes--coping with ineffective hematopoiesis. N Engl J Med. 2005 Feb 10;352(6):536-8. doi: 10.1056/NEJMp048266. No abstract available.
• Background Musto P, Falcone A, Sanpaolo G, Bodenizza C, La Sala A, Perla G, Carella AM. Efficacy of a single, weekly dose of recombinant erythropoietin in myelodysplastic syndromes. Br J Haematol. 2003 Jul;122(2):269-71. doi: 10.1046/j.1365-2141.2003.04435.x.
• Background Bowen D, Hyslop A, Keenan N, Groves M, Culligan D, Johnson P, Shaw A, Geddes F, Evans P, Porter J, Cavill I. Predicting erythroid response to recombinant erythropoietin plus granulocyte colony-stimulating factor therapy following a single subcutaneous bolus in patients with myelodysplasia. Haematologica. 2006 May;91(5):709-10.
• Background 33. Mundle S, Lefebvre P, Duh MS, et al. Erythroid response (ER) rates in myelodysplastic syndromes (MDS) patients treated with epoetin alfa (EPO) or darbepoetin alfa (DARB) using International Working Group response criteria (IWGc): Comparative meta-analysis. Blood 2006; 108; 2672 (abstr
• Background Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL, McIntyre HJ, Fernando IJ, Backstrom JT, Beach CL. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009 Apr 10;27(11):1850-6. doi: 10.1200/JCO.2008.17.1058. Epub 2009 Mar 2.

Drugs

Indications