Treatment of High Risk Myelodysplastic Syndromes (MDS) Not Candidates for Allogeneic Transplantation of Hematopoietic Progenitors (ALO-HSCT)

NCT04602273 | Unknown

• 1 other identifier: CET-AZA-2016-01
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

An observational, non-interventional, prospective and multicenter study of Azacitidine in newly diagnosed High Risk Myelodysplastic Syndromes. Primary objectives are to asses mutational status of target genes by Next Generation Sequencing, to evaluate prognostic value of geriatric assessment scales and to evaluate overall survival. The main hypothesis is that mutation status of target genes and geriatric scales have statistical significant impact on overall survival. Study time points will be at diagnosis, 6, 12, 18 and 24 months, always taking into account the routine clinical practice, when sample to assess mutational status will be collected. Geriatric assessment will only be performed at diagnosis. Upon the signature of informed consent and the checking of inclusion criteria, patients will receive treatment with Azacitidine 75 mg/sqm on a 28 days based cycles (both 7-0-0 and 5-0-2 regimens are allowed) until disease progression, unacceptable toxicity or investigator decision. 150 patients are expected to be recruited at study sites.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (4)

• Overall Survival (OS)

  5- year overall survival

• Progression Free Survival (PFS)

  5-year progression free survival

• Overall Response Rate (OOR)

  12 months OOR

• Treatment-Emergent Adverse Events Rate (TEAE)

  12 Months TEAE rate

Study Arms (1)

High Risk MDS

New diagnosed patients treated with Azacitidine 75 mg/sqm SC QD on a 28 days based cycles (both 7-0-0 and 5-0-2 regimens are allowed) until disease progression, unacceptable toxicity, death or investigator decision

Drug: Azacitidine Injection [Vidaza]

Interventions

Azacitidine Injection [Vidaza] DRUG

High Risk MDS

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

Newly diagnosed High-Risk Myelodysplastic Syndrome

You may qualify if:

• Patients diagnosed with myelodysplastic syndrome (MDS) according to WHO criteria, including non-proliferative chronic myelomonocytic leukemia (CMML) that is considered high risk, and not candidates for transplantation.
• High-risk MDS: (following the Grupo Español Síndrome Mielodisplásico, GESDM MDS guides) and the recommendations of Valcárcel, D. et al).
• Median expected OS less than 30 months. Intermediate-2 or high risk IPSS and / or high or very high risk WPSS and / or high or very high risk IPSSS-R.
• IPSS of intermediate risk and / or WPSS of intermediate risk and / or IPSS-R of intermediate risk that present at least one of the following characteristics:
• Cytogenetic abnormality of the IPSS-R high or very high cytogenetic risk group Platelet count \<30 x10E9/l Neutrophil count \<0.5 x 10E9 / l Presence of dense and diffuse myelofibrosis, with or without collagen formation (grades 2-3 of the European consensus) Category 3 of the LRSS score (MD Anderson low risk score system)
• Patient diagnosed with LAM de novo according to WHO criteria, with 20-30% blasts count in bone marrow, trilineal dysplasia and more than 70 years and not candidate for intensive chemotherapy.
• Willing to provide voluntary written informed consent

You may not qualify if:

• Serious active medical condition, not related to MDS, that could limit patient compliance and follow-up or that, in the Investigator's opinion,could compromise the patient's safety.
• Presence of other active malignant disease
• Organic function parameters: (except when the alteration is due to MDS) Hepatic: Bilirubin\> 2 x upper limit of normal (ULN) Renal: Creatinine\> 2 x upper limit of normal (ULN)
• Ejection fraction (\<40%) and / or symptomatic heart failure.
• Leukaemia secondary to Myeloproliferative Syndrome.
• Serious psychiatric or neurological disease.
• Positive Serology for HIV.
• Proliferative CMML

Sponsors & Collaborators

• Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias: lead
• Hospital Son Llatzer: collaborator
• Germans Trias i Pujol Hospital: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Son Llàtzer

Palma, Balearic Islands, 07198, Spain

RECRUITING

Related Publications (17)

• Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009 Nov 5;361(19):1872-85. doi: 10.1056/NEJMra0902908. No abstract available.

  PMID: 19890130 BACKGROUND

• Germing U, Strupp C, Kundgen A, Bowen D, Aul C, Haas R, Gattermann N. No increase in age-specific incidence of myelodysplastic syndromes. Haematologica. 2004 Aug;89(8):905-10.

  PMID: 15339672 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.

  PMID: 15703418 BACKGROUND

• Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul 30;114(5):937-51. doi: 10.1182/blood-2009-03-209262. Epub 2009 Apr 8.

  PMID: 19357394 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

• Fega KR, Abel GA, Motyckova G, Sherman AE, DeAngelo DJ, Steensma DP, Galinsky I, Wadleigh M, Stone RM, Driver JA. Non-hematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults. J Geriatr Oncol. 2015 Jul;6(4):288-98. doi: 10.1016/j.jgo.2015.05.003. Epub 2015 Jun 11.

  PMID: 26073533 BACKGROUND

• Hamaker ME, Mitrovic M, Stauder R. The G8 screening tool detects relevant geriatric impairments and predicts survival in elderly patients with a haematological malignancy. Ann Hematol. 2014 Jun;93(6):1031-40. doi: 10.1007/s00277-013-2001-0. Epub 2014 Feb 2.

  PMID: 24488257 BACKGROUND

• Bonanad S, De la Rubia J, Gironella M, Perez Persona E, Gonzalez B, Fernandez Lago C, Arnan M, Zudaire M, Hernandez Rivas JA, Soler A, Marrero C, Olivier C, Altes A, Valcarcel D, Hernandez MT, Oiartzabal I, Fernandez Ordono R, Arnao M, Esquerra A, Sarra J, Gonzalez-Barca E, Gonzalez J, Calvo X, Nomdedeu M, Garcia Guinon A, Ramirez Payer A, Casado A, Lopez S, Duran M, Marcos M, Cruz-Jentoft AJ; GAH Group. Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale. J Geriatr Oncol. 2015 Sep;6(5):353-61. doi: 10.1016/j.jgo.2015.03.003. Epub 2015 Jun 29.

  PMID: 26139300 BACKGROUND

• 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.

  PMID: 18443215 BACKGROUND

• Klepin HD. Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly. Clin Geriatr Med. 2016 Feb;32(1):155-73. doi: 10.1016/j.cger.2015.08.010.

  PMID: 26614866 BACKGROUND

• Xicoy B, Jimenez MJ, Garcia O, Bargay J, Martinez-Robles V, Brunet S, Arilla MJ, Perez de Oteyza J, Andreu R, Casano FJ, Cervero CJ, Bailen A, Diez M, Gonzalez B, Vicente AI, Pedro C, Bernal T, Luno E, Cedena MT, Palomera L, Simiele A, Calvo JM, Marco V, Gomez E, Gomez M, Gallardo D, Munoz J, de Paz R, Grau J, Ribera JM, Benlloch LE, Sanz G. Results of treatment with azacitidine in patients aged >/= 75 years included in the Spanish Registry of Myelodysplastic Syndromes. Leuk Lymphoma. 2014 Jun;55(6):1300-3. doi: 10.3109/10428194.2013.834532. Epub 2013 Sep 16.

  PMID: 23952246 BACKGROUND

• Gangat N, Patnaik MM, Tefferi A. Myelodysplastic syndromes: Contemporary review and how we treat. Am J Hematol. 2016 Jan;91(1):76-89. doi: 10.1002/ajh.24253.

  PMID: 26769228 BACKGROUND

• Bejar R, Lord A, Stevenson K, Bar-Natan M, Perez-Ladaga A, Zaneveld J, Wang H, Caughey B, Stojanov P, Getz G, Garcia-Manero G, Kantarjian H, Chen R, Stone RM, Neuberg D, Steensma DP, Ebert BL. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014 Oct 23;124(17):2705-12. doi: 10.1182/blood-2014-06-582809. Epub 2014 Sep 15.

  PMID: 25224413 BACKGROUND

• Itzykson R, Kosmider O, Cluzeau T, Mansat-De Mas V, Dreyfus F, Beyne-Rauzy O, Quesnel B, Vey N, Gelsi-Boyer V, Raynaud S, Preudhomme C, Ades L, Fenaux P, Fontenay M; Groupe Francophone des Myelodysplasies (GFM). Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia. 2011 Jul;25(7):1147-52. doi: 10.1038/leu.2011.71. Epub 2011 Apr 15.

  PMID: 21494260 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

• Deschler B, Ihorst G, Platzbecker U, Germing U, Marz E, de Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lubbert M. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013 Feb;98(2):208-16. doi: 10.3324/haematol.2012.067892. Epub 2012 Aug 8.

  PMID: 22875615 BACKGROUND

• Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. doi: 10.1182/blood-2005-05-2004. Epub 2005 Jun 30.

  PMID: 15994282 BACKGROUND

Related Links

• Grupo Español de Sindrome Mielodiplásico (GESMD) MDS treatment guides

Biospecimen

Retention: SAMPLES WITH DNA

3 ml Bone Marrow Aspirate samples will be processed and stored at: Laboratorio de Hematología Primera Planta Edificio General ICO - Hospital Germans Trias i Pujol Ctra. Canyet s/n 08916 Badalona

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Joan Bargay, MD PhD

  Hospital Son Llatzer

  PRINCIPAL INVESTIGATOR

• Lurdes Zamora, PhD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joan Bargay, MD PhD

CONTACT

34 871 202158; jbargay@hsll.es

Lurdes Zamora, PhD

CONTACT

+34 93 4978868; lzamora@iconcologia.net

Study Design

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

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: October 26, 2020
• Study Start: December 12, 2016
• Primary Completion: November 1, 2020
• Study Completion: June 30, 2021
• Last Updated: October 26, 2020

Record last verified: 2020-10

Locations

ES (1)