An European Platform for Translational Research in Myelodysplastic Syndromes

NCT04174547 | Unknown

• 1 other identifier: TRS-2018-00000745
• Study Type: observational
• Target: 8,670
• Locations: 4 countries
• Sites: 4

Brief Summary

Rationale Myelodysplastic syndromes (MDS) are rare cancers with unmet medical needs. Study of MDS has been rapidly transformed by genome characterization. The investigators hypothesize that comprehensive analyses of large patient population will allow to correctly estimate the effect of each mutation on clinical outcomes, and that niche factors and immune dysfunctions may influence the development of MDS, clonal evolution and response to treatments Aims 1- Investigate gene mutations, niche factors and immune dysfunctions influencing the development of MDS, and define biomarkers for early identification of individuals at risk; 2- Develop prognostic models for MDS patients through integration of comprehensive genomic/clinical information; 3- Define biomarkers to better stratify the individual probability of response to specific treatments Methods EuroBloodNet, the European Reference Network in rare hematological diseases, will provide a basis for research activities. Study of genomic features of clonal dominance in elderly subjects enrolled in large population-based studies and description of the dynamics of clonal establishment and evolution; study of bone marrow microenvironment to identify immune dysfunctions influencing MDS development. Development of inclusive statistical models to accurately predict clinical outcome at individual level, based on large MDS populations with comprehensive genomic/clinical data. Finally, analysis of mutational screening and immune profiles from patients enrolled in prospective trials, to provide evidence on genetic/immunologic profiles associated with probability of response to specific compounds Expected results To characterize how clonal hematopoiesis relates to the induction of MDS clinical phenotype, and to test the utility of gene sequencing to detect subjects at risk of developing MDS. To define effective prognostic systems and biomarkers to stratify the individual probability of response to treatment

Conditions

Myelodysplastic Syndromes

Keywords

Somatic mutations; Clonal hematopoiesis; Biomarkers; Immune escape; Innovative predictive models; EuroBloodNet

Outcome Measures

Primary Outcomes (4)

• DNA mutations in hematopoietic cells

  The investigotors will study the prevalence and type of somatic mutations by a low-cost, high-throughput platform including 72 genes, relevant in myeloid neoplasms.

  0-24 months

• RNA expression on hematopoietic progenitors and mesenchymal stromal cells

  The investigators will study the genes diffentially expressed between cell populations of interest and normal controls

  6-24 months

• Predictive biomarkers for survival and response to treatment

  The investigators will define, by innovative bayesian and clustering models, independent clinical and molecular factors associated to the probability of survival and response to specific treatments.

  0-30 months

• Frequency and function of T lymphocytes, NK cells and ILC cells

  The investigators will analyse by flow-cytometry the frequency of T lymphocytes, NK cells and ILC cells during different disease stages and in response to therapy. Complementary immunoassays based on Luminex technology will be used to quantify secretory proteins (cytokines, chemokines, growth factors).

  6-30 motnhs

Study Arms (3)

Clonal hematopoiesis (AIM 1)

The investigators will analyze the genomic features of clonal dominance and ineffective hematopoiesis in elderly subjects enrolled in two population-based studies: "Health and Anemia" study \[Haematologica 2010;95:1849\], and "Monzino 80-plus" study \[BMC Neurol.2011;11:54, validation cohort\]. Overall in 5000 subjects aged \>65y peripheral blood samples (in some cases collected at different time points) will be available for biological investigations.

Innovative predictive models in MDS (AIM2)

The investigators will base on large retrospectove adult MDS population with comprehensive genomic and clinical data available within EuroBloodNet network (data on 3000 patients will be available), to accurately predict clinical outcomes in MDS at individual-patient level. The investigators plan to define 2 homogenous clinical cohorts (learning and testing cohort at 2:1 ratio) in order to define distinct patterns and genetic groups within MDS and to independently validate their predictive value.

Predictive biomarkers in MDS (AIM3)

The investigators will analyze MDS patients enrolled in prospective clinical trials conducted within the EuroBloodNet network. Overall 350 patients treated with azacitidine from prospective studies (VidazaAllotrial, RELAZA02 trial, AZA-Ida study, intensive AZA study) will be available for biological investigations to define biomarkers associated with clinical response. Validation of biomarkers will then be performed in an independent cohort including 320 patients (AZA-PLUS trial). In all these studies, biobanking of bone marrow (BM) and peripheral blood (PB) samples has been systematically performed, providing a unique resource to be investigated within this proposal.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

AIM 1 Individuals enrolled in the population-based "Health and Anemia" and "Monzino 80+" studies, with biological samples available at prevalence day AIM 2 Patients receiving a diagnosis of MDS within EuroBloodNet clinical network, for which complete information on clinical and DNA mutational screening data is available AIM 3 * Testing cohort: MDS patients treated with HMAs within prospective clinical trials (VidazaAllotrial, RELAZA02 trial, AZA-Ida study, intensive AZA study), with biological samples availability * Validation cohort: adults MDS patients treated with HMAs within the prospective clinical trial AZA-PLUS, with biological samples availability

You may qualify if:

• \- Individuals aged 65 years or older from population-based studies (retrospective cohort)

You may not qualify if:

• \- lack of biological samples availability
• AIM 2
• \- adults patients (\>18 years) with a diagnosis of MDS according to WHO criteria (retrospective cohort)
• \- lack of availability of information on clinical and DNA mutational screening data
• AIM 3
• \- adults patients (\>18 years) with a diagnosis of MDS according to WHO criteria and treated with HMAs
• \- lack of biological samples availability

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (4)

Service d'hématologie séniors - Hôpital St Louis / Université Paris 7

Paris, 75475, France

RECRUITING

University of Leipzig Medical Center

Leipzig, 04103, Germany

RECRUITING

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

RECRUITING

Josep Carreras Leukaemia Research Institute (IJC)

Barcelona, 08916, Spain

RECRUITING

Related Publications (33)

• Ades L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014 Jun 28;383(9936):2239-52. doi: 10.1016/S0140-6736(13)61901-7. Epub 2014 Mar 21.

  PMID: 24656536 BACKGROUND

• Malcovati L, Hellstrom-Lindberg E, Bowen D, Ades L, Cermak J, Del Canizo C, Della Porta MG, Fenaux P, Gattermann N, Germing U, Jansen JH, Mittelman M, Mufti G, Platzbecker U, Sanz GF, Selleslag D, Skov-Holm M, Stauder R, Symeonidis A, van de Loosdrecht AA, de Witte T, Cazzola M; European Leukemia Net. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013 Oct 24;122(17):2943-64. doi: 10.1182/blood-2013-03-492884. Epub 2013 Aug 26.

  PMID: 23980065 BACKGROUND

• Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstocker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012 Sep 20;120(12):2454-65. doi: 10.1182/blood-2012-03-420489. Epub 2012 Jun 27.

  PMID: 22740453 BACKGROUND

• Schanz J, Tuchler H, Sole F, Mallo M, Luno E, Cervera J, Granada I, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstocker M, Nosslinger T, Valent P, Giagounidis A, Aul C, Lubbert M, Stauder R, Krieger O, Garcia-Manero G, Faderl S, Pierce S, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012 Mar 10;30(8):820-9. doi: 10.1200/JCO.2011.35.6394. Epub 2012 Feb 13.

  PMID: 22331955 BACKGROUND

• Nomdedeu M, Calvo X, Pereira A, Carrio A, Sole F, Luno E, Cervera J, Vallespi T, Munoz C, Gomez C, Arias A, Such E, Sanz G, Grau J, Insunza A, Calasanz MJ, Ardanaz MT, Hernandez-Rivas JM, Azaceta G, Alvarez S, Sanchez J, Martin ML, Bargay J, Gomez V, Cervero CJ, Allegue MJ, Collado R, Campo E, Esteve J, Nomdedeu B, Costa D; Spanish Group of Myelodysplastic Syndromes. Prognostic impact of chromosomal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemia patients. A study by the spanish group of myelodysplastic syndromes. Genes Chromosomes Cancer. 2016 Apr;55(4):322-7. doi: 10.1002/gcc.22333. Epub 2015 Dec 22.

  PMID: 26690722 BACKGROUND

• Schanz J, Tuchler H, Sole F, Mallo M, Luno E, Cervera J, Grau J, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstocker M, Nosslinger T, Valent P, Giagounidis A, Aul C, Lubbert M, Stauder R, Krieger O, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D. Monosomal karyotype in MDS: explaining the poor prognosis? Leukemia. 2013 Oct;27(10):1988-95. doi: 10.1038/leu.2013.187. Epub 2013 Jun 21.

  PMID: 23787396 BACKGROUND

• Valcarcel D, Adema V, Sole F, Ortega M, Nomdedeu B, Sanz G, Luno E, Canizo C, de la Serna J, Ardanaz M, Marco V, Collado R, Grau J, Montoro J, Mallo M, Vallespi T. Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome. J Clin Oncol. 2013 Mar 1;31(7):916-22. doi: 10.1200/JCO.2012.41.6073. Epub 2013 Jan 14.

  PMID: 23319689 BACKGROUND

• Della Porta MG, Alessandrino EP, Bacigalupo A, van Lint MT, Malcovati L, Pascutto C, Falda M, Bernardi M, Onida F, Guidi S, Iori AP, Cerretti R, Marenco P, Pioltelli P, Angelucci E, Oneto R, Ripamonti F, Bernasconi P, Bosi A, Cazzola M, Rambaldi A; Gruppo Italiano Trapianto di Midollo Osseo. Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R. Blood. 2014 Apr 10;123(15):2333-42. doi: 10.1182/blood-2013-12-542720. Epub 2014 Feb 20.

  PMID: 24558201 BACKGROUND

• Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, Yoon CJ, Ellis P, Wedge DC, Pellagatti A, Shlien A, Groves MJ, Forbes SA, Raine K, Hinton J, Mudie LJ, McLaren S, Hardy C, Latimer C, Della Porta MG, O'Meara S, Ambaglio I, Galli A, Butler AP, Walldin G, Teague JW, Quek L, Sternberg A, Gambacorti-Passerini C, Cross NC, Green AR, Boultwood J, Vyas P, Hellstrom-Lindberg E, Bowen D, Cazzola M, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886. Epub 2013 Sep 12.

  PMID: 24030381 BACKGROUND

• Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, Pellagatti A, Wainscoat JS, Hellstrom-Lindberg E, Gambacorti-Passerini C, Godfrey AL, Rapado I, Cvejic A, Rance R, McGee C, Ellis P, Mudie LJ, Stephens PJ, McLaren S, Massie CE, Tarpey PS, Varela I, Nik-Zainal S, Davies HR, Shlien A, Jones D, Raine K, Hinton J, Butler AP, Teague JW, Baxter EJ, Score J, Galli A, Della Porta MG, Travaglino E, Groves M, Tauro S, Munshi NC, Anderson KC, El-Naggar A, Fischer A, Mustonen V, Warren AJ, Cross NC, Green AR, Futreal PA, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011 Oct 13;365(15):1384-95. doi: 10.1056/NEJMoa1103283. Epub 2011 Sep 26.

  PMID: 21995386 BACKGROUND

• Della Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, Sole F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstocker M, Sekeres MA, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D, Greenberg PL, Cazzola M. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia. 2015 Jul;29(7):1502-13. doi: 10.1038/leu.2015.55. Epub 2015 Feb 27.

  PMID: 25721895 BACKGROUND

• Della Porta MG, Travaglino E, Boveri E, Ponzoni M, Malcovati L, Papaemmanuil E, Rigolin GM, Pascutto C, Croci G, Gianelli U, Milani R, Ambaglio I, Elena C, Ubezio M, Da Via' MC, Bono E, Pietra D, Quaglia F, Bastia R, Ferretti V, Cuneo A, Morra E, Campbell PJ, Orazi A, Invernizzi R, Cazzola M; Rete Ematologica Lombarda (REL) Clinical Network. Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia. 2015 Jan;29(1):66-75. doi: 10.1038/leu.2014.161. Epub 2014 May 20.

  PMID: 24935723 BACKGROUND

• Della Porta MG, Jackson CH, Alessandrino EP, Rossi M, Bacigalupo A, van Lint MT, Bernardi M, Allione B, Bosi A, Guidi S, Santini V, Malcovati L, Ubezio M, Milanesi C, Todisco E, Voso MT, Musto P, Onida F, Iori AP, Cerretti R, Grillo G, Molteni A, Pioltelli P, Borin L, Angelucci E, Oldani E, Sica S, Pascutto C, Ferretti V, Santoro A, Bonifazi F, Cazzola M, Rambaldi A. Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System. Leukemia. 2017 Nov;31(11):2449-2457. doi: 10.1038/leu.2017.88. Epub 2017 Mar 21.

  PMID: 28321120 BACKGROUND

• Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014 Dec 25;371(26):2488-98. doi: 10.1056/NEJMoa1408617. Epub 2014 Nov 26.

  PMID: 25426837 BACKGROUND

• Weidner H, Rauner M, Trautmann F, Schmitt J, Balaian E, Mies A, Helas S, Baschant U, Khandanpour C, Bornhauser M, Hofbauer LC, Platzbecker U. Myelodysplastic syndromes and bone loss in mice and men. Leukemia. 2017 Apr;31(4):1003-1007. doi: 10.1038/leu.2017.7. Epub 2017 Jan 11. No abstract available.

  PMID: 28074069 BACKGROUND

• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21.

  PMID: 19230772 BACKGROUND

• Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, Muus P, Te Boekhorst P, Sanz G, Del Canizo C, Guerci-Bresler A, Nilsson L, Platzbecker U, Lubbert M, Quesnel B, Cazzola M, Ganser A, Bowen D, Schlegelberger B, Aul C, Knight R, Francis J, Fu T, Hellstrom-Lindberg E; MDS-004 Lenalidomide del5q Study Group. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011 Oct 6;118(14):3765-76. doi: 10.1182/blood-2011-01-330126. Epub 2011 Jul 13.

  PMID: 21753188 BACKGROUND

• Mallo M, Luno E, Sanzo C, Cervera J, Haase D, Schanz J, Garcia-Manero G, del Canizo C, Sanz GF, Sole F. Clinical impact of the clone size in MDS cases with monosomy 7 or 7q deletion, trisomy 8, 20q deletion and loss of Y chromosome. Leuk Res. 2011 Jun;35(6):834-6. doi: 10.1016/j.leukres.2011.01.003. Epub 2011 Jan 26.

  PMID: 21269692 BACKGROUND

• Della Porta MG, Galli A, Bacigalupo A, Zibellini S, Bernardi M, Rizzo E, Allione B, van Lint MT, Pioltelli P, Marenco P, Bosi A, Voso MT, Sica S, Cuzzola M, Angelucci E, Rossi M, Ubezio M, Malovini A, Limongelli I, Ferretti VV, Spinelli O, Tresoldi C, Pozzi S, Luchetti S, Pezzetti L, Catricala S, Milanesi C, Riva A, Bruno B, Ciceri F, Bonifazi F, Bellazzi R, Papaemmanuil E, Santoro A, Alessandrino EP, Rambaldi A, Cazzola M. Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients With Myelodysplastic Syndromes Treated With Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol. 2016 Oct 20;34(30):3627-3637. doi: 10.1200/JCO.2016.67.3616.

  PMID: 27601546 BACKGROUND

• Gerstung M, Pellagatti A, Malcovati L, Giagounidis A, Porta MG, Jadersten M, Dolatshad H, Verma A, Cross NC, Vyas P, Killick S, Hellstrom-Lindberg E, Cazzola M, Papaemmanuil E, Campbell PJ, Boultwood J. Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes. Nat Commun. 2015 Jan 9;6:5901. doi: 10.1038/ncomms6901.

  PMID: 25574665 BACKGROUND

• Gerstung M, Papaemmanuil E, Martincorena I, Bullinger L, Gaidzik VI, Paschka P, Heuser M, Thol F, Bolli N, Ganly P, Ganser A, McDermott U, Dohner K, Schlenk RF, Dohner H, Campbell PJ. Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nat Genet. 2017 Mar;49(3):332-340. doi: 10.1038/ng.3756. Epub 2017 Jan 16.

  PMID: 28092685 BACKGROUND

• Schneider RK, Adema V, Heckl D, Jaras M, Mallo M, Lord AM, Chu LP, McConkey ME, Kramann R, Mullally A, Bejar R, Sole F, Ebert BL. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS. Cancer Cell. 2014 Oct 13;26(4):509-20. doi: 10.1016/j.ccr.2014.08.001. Epub 2014 Sep 18.

  PMID: 25242043 BACKGROUND

• Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, Radsak M, Wolff T, Zhang X, Laadem A, Sherman ML, Attie KM, Giagounidis A. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017 Oct;18(10):1338-1347. doi: 10.1016/S1470-2045(17)30615-0. Epub 2017 Sep 1.

  PMID: 28870615 BACKGROUND

• Platzbecker U, Hofbauer LC, Ehninger G, Holig K. The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes. Leuk Res. 2012 May;36(5):525-36. doi: 10.1016/j.leukres.2012.01.006. Epub 2012 Feb 1.

  PMID: 22300879 BACKGROUND

• Platzbecker U, Schetelig J, Finke J, Trenschel R, Scott BL, Kobbe G, Schaefer-Eckart K, Bornhauser M, Itzykson R, Germing U, Beelen D, Ehninger G, Fenaux P, Deeg HJ, Ades L; German MDS Study; Cooperative Transplant Study Group; Fred Hutchinson Cancer Research Center; Groupe Francophone des Myelodysplasies. Allogeneic hematopoietic cell transplantation in patients age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine. Biol Blood Marrow Transplant. 2012 Sep;18(9):1415-21. doi: 10.1016/j.bbmt.2012.05.003. Epub 2012 May 11.

  PMID: 22579634 BACKGROUND

• Park S, Hamel JF, Toma A, Kelaidi C, Thepot S, Campelo MD, Santini V, Sekeres MA, Balleari E, Kaivers J, Sapena R, Gotze K, Muller-Thomas C, Beyne-Rauzy O, Stamatoullas A, Kotsianidis I, Komrokji R, Steensma DP, Fensterl J, Roboz GJ, Bernal T, Ramos F, Calabuig M, Guerci-Bresler A, Bordessoule D, Cony-Makhoul P, Cheze S, Wattel E, Rose C, Vey N, Gioia D, Ferrero D, Gaidano G, Cametti G, Pane F, Sanna A, Germing U, Sanz GF, Dreyfus F, Fenaux P. Outcome of Lower-Risk Patients With Myelodysplastic Syndromes Without 5q Deletion After Failure of Erythropoiesis-Stimulating Agents. J Clin Oncol. 2017 May 10;35(14):1591-1597. doi: 10.1200/JCO.2016.71.3271. Epub 2017 Mar 28.

  PMID: 28350519 BACKGROUND

• Lamarque M, Raynaud S, Itzykson R, Thepot S, Quesnel B, Dreyfus F, Rauzy OB, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Visanica S, Stamatoullas A, Fenaux P, Ades L. The revised IPSS is a powerful tool to evaluate the outcome of MDS patients treated with azacitidine: the GFM experience. Blood. 2012 Dec 13;120(25):5084-5. doi: 10.1182/blood-2012-09-453555. No abstract available.

  PMID: 23243156 BACKGROUND

• Itzykson R, Thepot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Salanoubat C, Visanica S, Stamatoullas A, Isnard F, Marfaing-Koka A, de Botton S, Chelghoum Y, Taksin AL, Plantier I, Ame S, Boehrer S, Gardin C, Beach CL, Ades L, Fenaux P; Groupe Francophone des Myelodysplasies(GFM). Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011 Jan 13;117(2):403-11. doi: 10.1182/blood-2010-06-289280. Epub 2010 Oct 12.

  PMID: 20940414 BACKGROUND

• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. doi: 10.1200/JCO.2009.23.8329. Epub 2009 Dec 21.

  PMID: 20026804 BACKGROUND

• Mallo M, Del Rey M, Ibanez M, Calasanz MJ, Arenillas L, Larrayoz MJ, Pedro C, Jerez A, Maciejewski J, Costa D, Nomdedeu M, Diez-Campelo M, Lumbreras E, Gonzalez-Martinez T, Marugan I, Such E, Cervera J, Cigudosa JC, Alvarez S, Florensa L, Hernandez JM, Sole F. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations. Br J Haematol. 2013 Jul;162(1):74-86. doi: 10.1111/bjh.12354. Epub 2013 Apr 25.

  PMID: 23614682 BACKGROUND

• Mekinian A, Grignano E, Braun T, Decaux O, Liozon E, Costedoat-Chalumeau N, Kahn JE, Hamidou M, Park S, Puechal X, Toussirot E, Falgarone G, Launay D, Morel N, Trouiller S, Mathian A, Gombert B, Schoindre Y, Lioger B, De Wazieres B, Amoura Z, Buchdaul AL, Georgin-Lavialle S, Dion J, Madaule S, Raffray L, Cathebras P, Piette JC, Rose C, Ziza JM, Lortholary O, Montestruc F, Omouri M, Denis G, Rossignol J, Nimubona S, Ades L, Gardin C, Fenaux P, Fain O. Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study. Rheumatology (Oxford). 2016 Feb;55(2):291-300. doi: 10.1093/rheumatology/kev294. Epub 2015 Sep 8.

  PMID: 26350487 BACKGROUND

• Fraison JB, Mekinian A, Grignano E, Kahn JE, Arlet JB, Decaux O, Denis G, Buchdahl AL, Omouri M, Maigne G, Aouba A, Leon N, Berthier S, Liozon E, Park S, Gardin C, Lortholary O, Rossignol J, Fenaux P, Fain O, Braun T. Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res. 2016 Apr;43:13-7. doi: 10.1016/j.leukres.2016.02.005. Epub 2016 Feb 20.

  PMID: 26922775 BACKGROUND

• Khaznadar Z, Boissel N, Agaugue S, Henry G, Cheok M, Vignon M, Geromin D, Cayuela JM, Castaigne S, Pautas C, Raffoux E, Lachuer J, Sigaux F, Preudhomme C, Dombret H, Dulphy N, Toubert A. Defective NK Cells in Acute Myeloid Leukemia Patients at Diagnosis Are Associated with Blast Transcriptional Signatures of Immune Evasion. J Immunol. 2015 Sep 15;195(6):2580-90. doi: 10.4049/jimmunol.1500262. Epub 2015 Aug 5.

  PMID: 26246143 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood and marrow samples

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Matteo Della Porta, MD

  HUMANITAS Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matteo Della Porta, MD

CONTACT

+39 02 8224 7668; matteo.della_porta@hunimed.eu

Maria Elena Bicchieri, PhD

CONTACT

marilena.bicchieri@cancercenter.humanitas.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 22, 2019
• Study Start: September 30, 2019
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2022
• Last Updated: November 22, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); DE (1); IT (1); ES (1)