A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care
A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)
1 other identifier
interventional
358
15 countries
108
Brief Summary
The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled. See study AZA PH GL 2003 CL 001 E for information about the extension to this study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2003
Typical duration for phase_3
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 31, 2003
CompletedStudy Start
First participant enrolled
November 1, 2003
CompletedFirst Posted
Study publicly available on registry
November 5, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2007
CompletedResults Posted
Study results publicly available
July 5, 2010
CompletedOctober 29, 2019
October 1, 2019
3.7 years
October 31, 2003
March 2, 2010
October 16, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
Kaplan-Meier Estimates for Median Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.
Day 1 (randomization) to 42 months
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.
Day 1 (randomization) to 42 months
Number of Participants Who Died
Count of participants who died during the study
42 months
Secondary Outcomes (12)
Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
Day 1 (randomization) to 42 months
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
Day 1 (randomization) to 42 months
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Day 1 (randomization) to 42 months
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Day 1 (randomization) to 42 months
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Day 1 (randomization) to 42 months
- +7 more secondary outcomes
Study Arms (2)
Azacitidine
EXPERIMENTALStudy Drug plus best supportive care. Treatment with erythropoietin was not permitted
Conventional Care
ACTIVE COMPARATORPhysician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted
Interventions
Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m\^2/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.
Physician Choice was one of three options: * Best supportive care (BSC) alone, * Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or * Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle). All three options included best supportive care
Eligibility Criteria
You may qualify if:
- Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High.
- Be 18 years of age or older
- Have a life expectancy of at least 3 months
- Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission
- Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory
- Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis)
- Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal
You may not qualify if:
- Secondary myelodysplastic syndromes (MDS)
- Prior treatment with azacitidine;
- Prior history of acute myeloid leukemia (AML);
- Malignant disease diagnosed within prior 12 months;
- Metastatic disease;
- Hepatic tumors;
- Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months;
- Prior transplantation or cytotoxic therapy to treat MDS;
- Serious medical illness likely to limit survival to 12 months or less;
- Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days;
- Active HIV, viral hepatitis type B or C;
- Treatment with investigational drugs during prior 30 days;
- Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (108)
University of Alabama School of Medicine
Birmingham, Alabama, 35294, United States
Indiana University Cancer Center
Indianapolis, Indiana, 46202, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mount Sinai Medical Center
New York, New York, 10029-6574, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Oregon Cancer Center
Portland, Oregon, 97201, United States
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, 15224, United States
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, 53226, United States
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
The Newcastle Mater Miseriecordiae Hospital
Warratah, New South Wales, 2298, Australia
Royal Brisbane Hospital
Hersten, Queensland, 4029, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Peter MacCallum Cancer Institute
East Melbourne, Victoria, 3002, Australia
Royal Melbourne Hospital
Melbourne, Victoria, 3050, Australia
The Alfred Hospital
Melbourne, Victoria, 3181, Australia
The Royal Perth Hospital
Perth, Western Australia, 6847, Australia
First Clinical Base - Clinic of Hematology, MHAT - Pleven
Pleven, 5800, Bulgaria
MHAT "St George" Clinic of Hematology, Plovdiv
Plovdiv, 4002, Bulgaria
III-rd Internal Department, District Dispensary for Oncology diseases with stationary(DDOncDIU)
Plovdiv, 4004, Bulgaria
National Centre of Hematology and Transfusiology, Sofia
Sofia, 1756, Bulgaria
Multiprofile Hospital for Active Treatment (MHAT), "St. Marina" Clinic of Hematology
Varna, 3010, Bulgaria
University Multiprofile Hospital for Active Treatment "Sveta Marina"
Varna, 9010, Bulgaria
Fakultni nemocnice Brno
Jihlavska, Brno, 639 00, Czechia
Fakultni nemocnice Hradec Kralove
Sokolska, Hradec Kralove, 500 05, Czechia
Fakultni Nemocnice Olomouc
Olomouc, 775 20, Czechia
Vseobecna Fakultni Nemocnice
Prague, 2 128 08, Czechia
Uslav Hematologie a Krevni Transfuze
Prague, 2 128 20, Czechia
Chu D'Angers
Angers, 49033, France
Hopital Beaujon
Clichy, 92110, France
Che De Lille
Lille, 59037, France
Hospital Edouard Herriot
Lyon, 69437, France
Institute Paoli Calmettes
Marseille, 13009, France
Chu De Nantes
Nantes, 44093, France
Hospital Saint Louis
Paris, 75010, France
Hopital Cochin
Paris, 75679, France
Centre Henri Becquerel
Rouen, 76038, France
Chu Purpan
Toulouse, 31059, France
Universitatsklinikum Benjamin Franklin
Hindenburgdamm, State of Berlin, D-12203, Germany
Universitatsklinikum Bonn
Bonn, 53105, Germany
Klinikum Chemnitz gGmbH
Chemnitz, 9113, Germany
Universitatsklinikum Carl Gustav Carus
Dresden, 1307, Germany
St Johannes Hospital
Duisburg, 47166, Germany
Heinrich-Heine University Dusseldorf
Düsseldorf, 40225, Germany
University Essen
Essen, 45147, Germany
Gerorg-August-Universitat Gottingen
Göttingen, 37075, Germany
Allgemeines Krankenhaus St. Georg
Hamburg, D-20099, Germany
Universitatsklinikum Hambur-Eppendorf
Hamburg, D-20246, Germany
Universitatsklinikum Kiel II
Kiel, D-24116, Germany
Universitatsklinikum Ulm
Ulm, 89070, Germany
University Hospital-Attikon
Haidari, Athens, 12462, Greece
University General Hospital of Heraklio Voutes
Heraklio, Crete, 71110, Greece
District General Hospital of Athens
Athens, 11527, Greece
General Hospital of Chest Disease
Athens, 11527, Greece
University General Hospital of Ioannina
Ioannina, 45500, Greece
University General Hospital of Patra Rio
Pátrai, 26500, Greece
Orszagos Gyogyintezeti Kozpont
Budapest, 1135, Hungary
University of Pecs, 1st Dept of Internal Medicine
Pécs, 7624, Hungary
University of Szeged, 2nd Department of Internal Medicine
Szeged, 6701, Hungary
Policlinico S. Orsola-Malpighi
Bologna, 40138, Italy
Universita di Firenze
Florence, 50139, Italy
Ospedale San Martino
Genova, I-16132, Italy
Instituto Nazionale Dei Tumori
Milan, 20133, Italy
Centro Oncologico Modenese
Modena, 41100, Italy
Ospedale San Eugenio
Roma, 00144, Italy
Policlinico Gemelli
Roma, 00168, Italy
Instituto Nazionale Tumori "Regina Elena"
Roma, 144, Italy
Ospedale Casa Sollievo Della Sofferenza - Irrc
San Giovanni Rotondo, 71013, Italy
Universita Degli Studi Di Sassari
Sassari, 7100, Italy
VU University Medical Center Amsterdam
Amsterdam, 1081 HV, Netherlands
Univ Hospital St. Radboud
Nijmejen, Netherlands
Samodzielny Publiczny Szpital Kliniczny Nr 1
Gdansk, 80-952, Poland
Wojewodzki Szpital Specjalistyczny
Lodz, 93-510, Poland
Samodzielny Publiczny Szpital Kliniczny
Lublin, 20081, Poland
Wojskowy Instytut Medyczny
Warsaw, 00-909, Poland
Samodzelny Publiczny Centralny Szpital Kliniczny
Warsaw, 02-097, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1
Wroclaw, 50-367, Poland
Burdenko Central Military Clinical Hospital
Moscow, 105299, Russia
Blokhin Cancer Research Center
Moscow, 115487, Russia
Scientific Haematology Center, Moscow
Moscow, 125167, Russia
Institute of Haematology & Blood Transfusion
Saint Petersburg, 193024, Russia
Pavlov State Medical University
Saint Petersburg, 197022, Russia
Pavlov State Medical University
Saint Petersburg, 197089, Russia
City Hospital #31
Saint Petersburg, 197110, Russia
Hospital Santa Creu I Sant Pau
Barcelona, 08025, Spain
Hospital Clinic
Barcelona, 08036, Spain
Hospital Universitario Germans Trias I Pujol
Barcelona, Spain
Hospital de Leon
León, 24071, Spain
Hospital Universitario De La Princesa
Madrid, 28006, Spain
Hospital Ramon Y Cajal
Madrid, 28034, Spain
Hospital La Paz, Madrid
Madrid, 28046, Spain
Hospital Clinico San Carlos
Madrid, 28048, Spain
Hospital Son Llatzer
Palma de Mallorca, 07198, Spain
Hospital Universitario Del Salamanca
Salamanca, 37007, Spain
Hospital Universitario La Fe
Valencia, 46009, Spain
Sahlgrenska University Hospital
Gothenburg, S-413 45, Sweden
Lund Universtiy Hospital
Lund, 22185, Sweden
University Hospital MAS
Malmo, S-205 02, Sweden
Huddinge University Hospital
Stockholm, 14186, Sweden
Uppsala University Hospital
Uppsala, S-751 85, Sweden
Royal Bournemouth General Hospital
Bournemouth, BH7 7DW, United Kingdom
St. Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
Kings College Hospital NHS Trust
London, United Kingdom
Christie Hospital
Manchester, M20 4BX, United Kingdom
Norfolk and Norwich University Hospital
Norwich, NR4 7UY, United Kingdom
John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
Royal Cornwall Hospital
Truro, TR1 3LJ, United Kingdom
Related Publications (6)
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: 20026804RESULTFenaux P, Gattermann N, Seymour JF, Hellstrom-Lindberg E, Mufti GJ, Duehrsen U, Gore SD, Ramos F, Beyne-Rauzy O, List A, McKenzie D, Backstrom J, Beach CL. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. Br J Haematol. 2010 Apr;149(2):244-9. doi: 10.1111/j.1365-2141.2010.08082.x. Epub 2010 Feb 5.
PMID: 20136825RESULTSantini V, Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Silverman LR, List A, Gore SD, Seymour JF, Backstrom J, Beach CL. Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*. Eur J Haematol. 2010 Aug;85(2):130-8. doi: 10.1111/j.1600-0609.2010.01456.x. Epub 2010 Apr 12.
PMID: 20394651RESULTSeymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellstrom-Lindberg E, Santini V, List AF, Gore SD, Backstrom J, McKenzie D, Beach CL. Effects of azacitidine compared with conventional care regimens in elderly (>/= 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol. 2010 Dec;76(3):218-27. doi: 10.1016/j.critrevonc.2010.04.005. Epub 2010 May 6.
PMID: 20451404RESULTFenaux 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: 19230772RESULTGore SD, Fenaux P, Santini V, Bennett JM, Silverman LR, Seymour JF, Hellstrom-Lindberg E, Swern AS, Beach CL, List AF. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. 2013 Jul;98(7):1067-72. doi: 10.3324/haematol.2012.074831. Epub 2013 Apr 12.
PMID: 23585522DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- CL Beach
- Organization
- Celgene Corporation
Study Officials
- STUDY DIRECTOR
CL Beach
Celgene Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 31, 2003
First Posted
November 5, 2003
Study Start
November 1, 2003
Primary Completion
July 1, 2007
Study Completion
July 1, 2007
Last Updated
October 29, 2019
Results First Posted
July 5, 2010
Record last verified: 2019-10