Collection of Biological Data With Potential Prognostic Relevance in Patients With MYELODYSPLASTIC SYNDROMES (O-MDS-Protocol)

The present study is designed to determine the mutational status of markers (TET2 and PLCb2, cytogenetic aberrations) together with methylation status of the above genes using bone marrow and matched buccal cell samples from MDS patients who necessitate to start a treatment (i.e. EPO, Lenalidomide, Azacytidine). All patients included in the study will be followed for at least 2 years.

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndrome

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Fortunato Morabito, MD; Phone Number: +390984681329; Email: omdsprotocol@fondazioneameliascorza.it
• Study Contact Backup: Name: Anna G Recchia, PhD; Phone Number: +390984681539; Email: omdsprotocol@fondazioneameliascorza.it

Study Locations

• Italy
  • Brescia, Italy
    • Not yet recruiting
    • U.O. Ematologia - A.O. Spedali Civili di Brescia
    • Contact: Giuseppe Rossi, MD; Phone Number: +390303996573; Email: ematologia@spedalicivili.brescia.it
    • Sub-Investigator: Giuseppe Rossi, MD
  • Brindisi, Italy
    • Not yet recruiting
    • Divisione di Ematologia Presidio Ospedaliero "A. Perrino"
    • Contact: Giovanni Quarta, MD; Phone Number: +390831537507; Email: quarta.gianni@gmail.com
    • Sub-Investigator: Giovanni Quarta, MD
  • Catania, Italy
    • Not yet recruiting
    • Divisione Clinicizzata di Ematologia con Trapianto di Midollo Osseo. Ospedale Ferrarotto. Azienda Policlinico
    • Contact: Giuseppe Palumbo, MD; Email: ga.palumbo@gmail.com
    • Sub-Investigator: Giuseppe Palumbo, MD
  • Catanzaro, Italy
    • Not yet recruiting
    • S.O.C. Ematologia Azienda Ospedaliera di Catanzaro"Pugliese-Ciaccio"
    • Contact: Domenico Magro, MD; Phone Number: +390961883120; Email: magro.dom@virgilio.it
    • Sub-Investigator: Domenico Magro, MD
  • Cosenza, Italy, 87100
    • Recruiting
    • Unità Operativa Complessa di Ematologia- Azienda Ospedaliera di Cosenza
    • Contact: Fortunato Morabito, MD; Phone Number: +390984681329; Email: omdsprotocol@fondazioneameliascorza.it
  • Matera, Italy
    • Not yet recruiting
    • Unità di Ematologia, Ospedale Madonna delle Grazie, ASM
    • Contact: Alberto Fragasso, MD; Email: alberto.fragasso@libero.it
    • Sub-Investigator: Alberto Fragasso, MD
  • Palermo, Italy
    • Not yet recruiting
    • Dipartimento di Oncologia, Oncoematologia e Unità Trapianto di Midollo Osseo, 'La Maddalena'
    • Contact: Maurizio Musso, MD; Phone Number: +390916806814; Email: mamusso@libero.it
    • Sub-Investigator: Maurizio Musso, MD
  • Pisa, Italy
    • Not yet recruiting
    • U.O. di Ematologia Azienda Ospedaliera Universitaria Pisana
    • Contact: Mario Petrini, MD
    • Contact: Sara Galimberti, MD; Email: s.galimberti@med.unipi.it
    • Sub-Investigator: Sara Galimberti, MD
  • Reggio Calabria, Italy
    • Not yet recruiting
    • Divisione Ematologia - Azienda Ospedaliera "Bianchi-Melacrino-Morelli"
    • Contact: Esther Oliva, MD; Email: estheroliva@hotmail.com
    • Sub-Investigator: Esther Oliva, MD
  • Roma, Italy, 00161
    • Not yet recruiting
    • Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza
    • Sub-Investigator: Giuliana Alimena, MD
    • Contact: Giuliana Alimena, MD; Email: alimena@bce.uniroma1.it
  • Roma, Italy
    • Not yet recruiting
    • U.O.C. di Ematologia - Policlinico Agostino Gemelli-
    • Contact: Maria T Voso, MD; Phone Number: 0039 0630154278; Email: mtvoso@rm.unicatt.it
    • Sub-Investigator: Maria T Voso, MD
  • L'Aquila
    • Coppito, L'Aquila, Italy, 67010
      • Not yet recruiting
      • U.O. Medicina Interna Universitaria 2 ed Ematologia Ospedale Civile San Salvatore
      • Contact: Alessandro Lucchesi, MD; Phone Number: +390862368589; Email: ale.lucchesi@gmail.com
      • Sub-Investigator: Alessandro Lucchesi, MD
  • Potenza
    • Rionero in Vulture, Potenza, Italy
      • Not yet recruiting
      • Unità di Ematologia e Trapianto di Midollo Osseo, IRCCS-CROB, Centro di Riferimento Oncologico della Basilicata
      • Sub-Investigator: Pellegrino Musto, MD
      • Contact: Pellegrino Musto, MD; Phone Number: +390972726225; Email: p.musto@crob.it
  • Roma
    • Rome, Roma, Italy, 00189
      • Not yet recruiting
      • U. O. C. Ematologia - Azienda Ospedaliera Sant'Andrea
      • Contact: Maria A Aloe Spiriti, MD; Phone Number: +390633775052; Email: aloespiritisapienza@gmail.com
      • Sub-Investigator: Maria A Aloe Spiriti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with MDS detected by current diagnostic techniques (i.e., peripheral blood cytopenia, bone marrow morphology, cytogenetics andFISH analysis).

Description

Inclusion Criteria:

• Written informed consent
• Patients diagnosed with MDS according to FAB, WHO and IPSS classifications
• All clinically treatable MDS patients with EPO or Lenalidomide or 5-Azacytidine;
• Hb < 10 g/dL
• Age ≥ 18 years
• Gender: Male or Female
• Sufficient amount of biological samples for molecular studies

Exclusion Criteria:

• Age <18 years
• Patients who do not require treatment on "watch and wait" strategy
• Insufficient amount of biological samples for molecular studies

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with MYELODYSPLASTIC SYNDROMES; Patients diagnosed with MDS according to FAB, WHO and IPSS classifications. Patients who necessitate to start a treatment (i.e. EPO, Lenalidomide, Azacytidine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analyze the incidence of TET2 gene mutations and Validation of the prognostic potential of TET2 mutations and MPLA screening	Analyze the incidence of TET2 gene mutations in a series of MDS patients and describe the clinical status of patients carrying mutations Validation of the prognostic potential of TET2 mutations and MPLA screening on: Response rate to treatment with Epo, Lenalidomide and Azacitidine; Progression Free Survival (PFS )	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of the prognostic potential of TET2 mutations	Validation of the prognostic potential of Tet2 mutations on: Overall Survival;; Validation of MLPA analyisis in the identification of cytogenetic abnormalities in MDS patients as a complementary screening tool;; Validation of the prognostic relevance of MLPA analysis	2 years

Collaborators and Investigators

• Sponsor: Fondazione Amelia Scorza Onlus
• Investigators: Principal Investigator: Fortunato Morabito, MD, Unità Operativa Complessa di Ematologia- Azienda Ospedaliera di Cosenza - Italy

Publications and helpful links

General Publications

• 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. Erratum In: Blood 1998 Feb 1;91(3):1100.
• 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.
• Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002 Oct 1;100(7):2292-302. doi: 10.1182/blood-2002-04-1199.
• Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, Edwards BK, List AF. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008 Jul 1;112(1):45-52. doi: 10.1182/blood-2008-01-134858. Epub 2008 Apr 28.
• Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009 May 15;324(5929):930-5. doi: 10.1126/science.1170116. Epub 2009 Apr 16.
• Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol. 1999 Dec;10(12):1419-32. doi: 10.1023/a:1008375931236.
• 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.
• Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lecluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguie F, Fontenay M, Vainchenker W, Bernard OA. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009 May 28;360(22):2289-301. doi: 10.1056/NEJMoa0810069.
• Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R, Huberman K, Thomas S, Dolgalev I, Heguy A, Paietta E, Le Beau MM, Beran M, Tallman MS, Ebert BL, Kantarjian HM, Stone RM, Gilliland DG, Crispino JD, Levine RL. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009 Jul 2;114(1):144-7. doi: 10.1182/blood-2009-03-210039. Epub 2009 May 6.
• Bacher U, Haferlach C, Schnittger S, Kohlmann A, Kern W, Haferlach T. Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies. Ann Hematol. 2010 Jul;89(7):643-52. doi: 10.1007/s00277-010-0920-6. Epub 2010 Mar 2.
• Couronne L, Lippert E, Andrieux J, Kosmider O, Radford-Weiss I, Penther D, Dastugue N, Mugneret F, Lafage M, Gachard N, Nadal N, Bernard OA, Nguyen-Khac F. Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias. Leukemia. 2010 Jan;24(1):201-3. doi: 10.1038/leu.2009.169. Epub 2009 Aug 27. No abstract available.
• Kosmider O, Gelsi-Boyer V, Cheok M, Grabar S, Della-Valle V, Picard F, Viguie F, Quesnel B, Beyne-Rauzy O, Solary E, Vey N, Hunault-Berger M, Fenaux P, Mansat-De Mas V, Delabesse E, Guardiola P, Lacombe C, Vainchenker W, Preudhomme C, Dreyfus F, Bernard OA, Birnbaum D, Fontenay M; Groupe Francophone des Myelodysplasies. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009 Oct 8;114(15):3285-91. doi: 10.1182/blood-2009-04-215814. Epub 2009 Aug 7.
• Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens-Linders E, van Hoogen P, van Kessel AG, Raymakers RA, Kamping EJ, Verhoef GE, Verburgh E, Hagemeijer A, Vandenberghe P, de Witte T, van der Reijden BA, Jansen JH. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009 Jul;41(7):838-42. doi: 10.1038/ng.391. Epub 2009 May 31.
• Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia. 2003 Mar;17(3):637-41. doi: 10.1038/sj.leu.2402834. No abstract available.
• Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007 Apr 15;109(8):1536-42. doi: 10.1002/cncr.22570.
• Malcovati L, Nimer SD. Myelodysplastic syndromes: diagnosis and staging. Cancer Control. 2008 Oct;15 Suppl:4-13. doi: 10.1177/107327480801504s02.
• Nie HH, H.H., Jenkins JG, Steinmrenner K, Bent DH., SPSS (Statistical Package for the Social Science). 1979, New York, NY: McGraw-Hill.
• Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y. LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res. 2002 Jul 15;62(14):4075-80.
• Sanz GF, Sanz MA, Greenberg PL. Prognostic factors and scoring systems in myelodysplastic syndromes. Haematologica. 1998 Apr;83(4):358-68.
• Sekeres M, Cosgrove D, Falco A. Managing patients with low-risk MDS. Clin Adv Hematol Oncol. 2006 Jul;4(7 Suppl 16):1-10; quiz 11-2.
• Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon, 2008.
• Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Gangat N, Finke CM, Schwager S, Mullally A, Li CY, Hanson CA, Mesa R, Bernard O, Delhommeau F, Vainchenker W, Gilliland DG, Levine RL. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia. 2009 May;23(5):905-11. doi: 10.1038/leu.2009.47. Epub 2009 Mar 5.
• Tefferi A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Patnaik MM, Hanson CA, Pardanani A, Gilliland DG, Levine RL. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia. 2009 Jul;23(7):1343-5. doi: 10.1038/leu.2009.59. Epub 2009 Mar 19. No abstract available.
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• Woo JG, Sun G, Haverbusch M, Indugula S, Martin LJ, Broderick JP, Deka R, Woo D. Quality assessment of buccal versus blood genomic DNA using the Affymetrix 500 K GeneChip. BMC Genet. 2007 Nov 8;8:79. doi: 10.1186/1471-2156-8-79.
• Saint-Martin C, Leroy G, Delhommeau F, Panelatti G, Dupont S, James C, Plo I, Bordessoule D, Chomienne C, Delannoy A, Devidas A, Gardembas-Pain M, Isnard F, Plumelle Y, Bernard O, Vainchenker W, Najman A, Bellanne-Chantelot C; French Group of Familial Myeloproliferative Disorders. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009 Aug 20;114(8):1628-32. doi: 10.1182/blood-2009-01-197525. Epub 2009 Jun 29.
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Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: February 7, 2011
• First Submitted That Met QC Criteria: February 7, 2011
• First Posted (Estimate): February 8, 2011

Study Record Updates

• Last Update Posted (Estimate): February 8, 2011
• Last Update Submitted That Met QC Criteria: February 7, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: O-MDS-PROTOCOL