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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04602273
• Other study ID #: CET-AZA-2016-01
• Status: Recruiting
• Start date: December 12, 2016
• Est. completion date: June 30, 2021

Study information

• Verified date: October 2020
• Source: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
• Contact: Joan Bargay, MD PhD
• Phone: 34 871 202158
• Email: jbargay[@]hsll.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 30, 2021
• Est. primary completion date: November 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Azacitidine Injection [Vidaza]

Locations

Country	Name	City	State
Spain	Son Llàtzer	Palma	Islas Baleares

Sponsors (4)

Lead Sponsor	Collaborator
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias	Celgene Corporation, Germans Trias i Pujol Hospital, Hospital Son Llatzer

Country where clinical trial is conducted

Spain, 

References & Publications (17)

Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-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. — View Citation

Bonanad S, De la Rubia J, Gironella M, Pérez Persona E, González B, Fernández Lago C, Arnan M, Zudaire M, Hernández Rivas JA, Soler A, Marrero C, Olivier C, Altés A, Valcárcel D, Hernández MT, Oiartzabal I, Fernández Ordoño R, Arnao M, Esquerra A, Sarrá J, González-Barca E, González J, Calvo X, Nomdedeu M, García Guiñón A, Ramírez Payer A, Casado A, López S, Durán 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. — View Citation

Cazzola M, Malcovati L. Myelodysplastic syndromes--coping with ineffective hematopoiesis. N Engl J Med. 2005 Feb 10;352(6):536-8. — View Citation

Deschler B, Ihorst G, Platzbecker U, Germing U, März E, de Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lübbert 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Germing U, Strupp C, Kündgen 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. — View Citation

Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé 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, Pfeilstöcker 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. Epub 2012 Jun 27. — View Citation

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. — View Citation

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, Adès 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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2005 Jun 30. — View Citation

Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009 Nov 5;361(19):1872-85. doi: 10.1056/NEJMra0902908. Review. — View Citation

Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-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. Review. — View Citation

Xicoy B, Jiménez MJ, García O, Bargay J, Martínez-Robles V, Brunet S, Arilla MJ, Pérez de Oteyza J, Andreu R, Casaño FJ, Cervero CJ, Bailén A, Díez M, González B, Vicente AI, Pedro C, Bernal T, Luño E, Cedena MT, Palomera L, Simiele A, Calvo JM, Marco V, Gómez E, Gómez M, Gallardo D, Muñoz 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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		5- year overall survival
Primary	Progression Free Survival (PFS)		5-year progression free survival
Primary	Overall Response Rate (OOR)		12 months OOR
Primary	Treatment-Emergent Adverse Events Rate (TEAE)		12 Months TEAE rate

External Links

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