A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care - Full Text View

Sponsor:	Celgene Corporation
Information provided by:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00071799

Purpose

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.

Condition	Intervention	Phase
Myelodysplastic Syndromes	Drug: Azacitidine Other: Physician Choice	Phase III

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	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)

Resource links provided by NLM:

Drug Information available for: Azacitidine

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

determine the effect of azacitidine + best supportive care (BSC), relative to conventional care regimens + BSC, on hematologic status & status according to International Working Group (IWG) criteria & episodes of infections requiring IV antibiotics; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
determine the time to relapse after CR or PR, or disease progression (according to IWG criteria), in MDS patients treated with azacitidine + BSC, as compared with patients receiving conventional care regimens + BSC; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
to determine the time to transformation to AML, in MDS patients treated with azacitidine plus best supportive care, as compared with patients receiving conventional care regimens plus best supportive care; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
to determine the effect of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care on time to AML transformation or death from any cause; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
to determine the safety and toxicity of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care in MDS patients. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment:	358
Study Start Date:	November 2003
Study Completion Date:	August 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Azacitidine Arm: Experimental Study Drug	Drug: Azacitidine 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.
Conventional Care: Active Comparator Physician choice of low dose cytarabine, standard chemotherapy or best supportive care consisting of blood products, growth factors, antibiotics	Other: Physician Choice Physician Choice of low dose cytarabine, standard chemotherapy, or best supportive care consisting of blood products, growth factors, antibiotics.

Arms

Assigned Interventions

Azacitidine Arm: Experimental

Study Drug

Drug: Azacitidine

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.

Conventional Care: Active Comparator

Physician choice of low dose cytarabine, standard chemotherapy or best supportive care consisting of blood products, growth factors, antibiotics

Other: Physician Choice

Physician Choice of low dose cytarabine, standard chemotherapy, or best supportive care consisting of blood products, growth factors, antibiotics.

Detailed Description:

Comparison/Control Interventions: Best supportive care, or low dose cytarabine plus best supportive care.

Duration of Intervention: Patients will be treated until death, withdrawal, or conclusion of the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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 MDS and a relatively high risk of 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

Exclusion Criteria:

Secondary MDS
Prior treatment with azacitidine;
Prior history of 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071799

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Locations

United States, Alabama
University of Alabama School of Medicine
Birmingham, Alabama, United States, 35294
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029-6574
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Oregon
Oregon Cancer Center
Portland, Oregon, United States, 97201
United States, Pennsylvania
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, United States, 15224
United States, Wisconsin
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Royal North Shore Hospital
St. Leonards, New South Wales, Australia, 2065
The Newcastle Mater Miseriecordiae Hospital
Warratah, New South Wales, Australia, 2298
Australia, Queensland
Royal Brisbane Hospital
Hersten, Queensland, Australia, 4029
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Peter MacCallum Cancer Institute
East Melbourne, Victoria, Australia, 3002
The Alfred Hospital
Melbourne, Victoria, Australia, 3181
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Australia, Western Australia
The Royal Perth Hospital
Perth, Western Australia, Australia, 6847
Bulgaria
First Clinical Base - Clinic of Hematology, MHAT - Pleven
Pleven, Bulgaria, 5800
MHAT "St George" Clinic of Hematology, Plovdiv
Plovdiv, Bulgaria, 4002
III-rd Internal Department, District Dispensary for Oncology diseases with stationary(DDOncDIU)
Plovdiv, Bulgaria, 4004
National Centre of Hematology and Transfusiology, Sofia
Sofia, Bulgaria, 1756
Multiprofile Hospital for Active Treatment (MHAT), "St. Marina" Clinic of Hematology
Varna, Bulgaria, 3010
University Multiprofile Hospital for Active Treatment "Sveta Marina"
Varna, Bulgaria, 9010
Czech Republic
Vseobecna Fakultni Nemocnice
Praha, Czech Republic, 2 128 08
Uslav Hematologie a Krevni Transfuze
Praha, Czech Republic, 2 128 20
Fakultni Nemocnice Olomouc
Olomouc, Czech Republic, 775 20
Czech Republic, Brno
Fakultni nemocnice Brno
Jihlavska, Brno, Czech Republic, 639 00
Czech Republic, Hradec Kralove
Fakultni nemocnice Hradec Kralove
Sokolska, Hradec Kralove, Czech Republic, 500 05
France
Chu D'Angers
Angers, France, 49033
Hopital Beaujon
Clichy, France, 92110
Institute Paoli Calmettes
Marseille, France, 13009
Hospital Edouard Herriot
Lyon, France, 69437
Che De Lille
Lille, France, 59037
Chu De Nantes
Nantes, France, 44093
Hopital Cochin
Paris, France, 75679
Hospital Saint Louis
Paris, France, 75010
Centre Henri Becquerel
Rouen, France, 76038
Chu Purpan
Toulouse, France, 31059
Germany
Universitatsklinikum Bonn
Bonn, Germany, 53105
Klinikum Chemnitz gGmbH
Chemnitz, Germany, 9113
Universitatsklinikum Carl Gustav Carus
Dresden, Germany, 1307
St Johannes Hospital
Duisburg, Germany, 47166
Heinrich-Heine University Dusseldorf
Dusseldorf, Germany, 40225
University Essen
Essen, Germany, 45147
Allgemeines Krankenhaus St. Georg
Hamburg, Germany, D-20099
Universitatsklinikum Hambur-Eppendorf
Hamburg, Germany, D-20246
Gerorg-August-Universitat Gottingen
Gottingen, Germany, 37075
Universitatsklinikum Kiel II
Kiel, Germany, D-24116
Universitatsklinikum Ulm
Ulm, Germany, 89070
Germany, Berlin
Universitatsklinikum Benjamin Franklin
Hindenburgdamm, Berlin, Germany, D-12203
Greece
District General Hospital of Athens
Athens, Greece, 11527
General Hospital of Chest Disease
Athens, Greece, 11527
University General Hospital of Ioannina
Ioannina, Greece, 45500
University General Hospital of Patra Rio
Patra, Greece, 26500
Greece, Athens
University Hospital-Attikon
Haidari, Athens, Greece, 12462
Greece, Crete
University General Hospital of Heraklio Voutes
Heraklio, Crete, Greece, 71110
Hungary
Orszagos Gyogyintezeti Kozpont
Budapest, Hungary, 1135
University of Pecs, 1st Dept of Internal Medicine
Pecs, Hungary, 7624
University of Szeged, 2nd Department of Internal Medicine
Szeged, Hungary, 6701
Italy
Policlinico S. Orsola-Malpighi
Bologna, Italy, 40138
Instituto Nazionale Tumori "Regina Elena"
Roma, Italy, 144
Ospedale San Martino
Genova, Italy, I-16132
Instituto Nazionale Dei Tumori
Milano, Italy, 20133
Centro Oncologico Modenese
Modena, Italy, 41100
Ospedale San Eugenio
Roma, Italy, 00144
Policlinico Gemelli
Roma, Italy, 00168
Universita di Firenze
Firenze, Italy, 50139
Ospedale Casa Sollievo Della Sofferenza - Irrc
San Giovanni Rotondo, Italy, 71013
Universita Degli Studi Di Sassari
Sassari, Italy, 7100
Netherlands
VU University Medical Center Amsterdam
Amsterdam, Netherlands, 1081 HV
Univ Hospital St. Radboud
Nijmejen, Netherlands
Poland
Samodzielny Publiczny Szpital Kliniczny
Lublin, Poland, 20081
Wojewodzki Szpital Specjalistyczny
Lodz, Poland, 93-510
Samodzielny Publiczny Szpital Kliniczny Nr 1
Gdansk, Poland, 80-952
Samodzelny Publiczny Centralny Szpital Kliniczny
Warszawa, Poland, 02-097
Wojskowy Instytut Medyczny
Warszawa, Poland, 00-909
Samodzielny Publiczny Szpital Kliniczny Nr 1
Wroclaw, Poland, 50-367
Russian Federation
Blokhin Cancer Research Center
Moscow, Russian Federation, 115487
Burdenko Central Military Clinical Hospital
Moscow, Russian Federation, 105299
Scientific Haematology Center, Moscow
Moscow, Russian Federation, 125167
Institute of Haematology & Blood Transfusion
St. Petersburg, Russian Federation, 193024
Pavlov State Medical University
St. Petersburg, Russian Federation, 197089
City Hospital #31
St. Petersburg, Russian Federation, 197110
Pavlov State Medical University
St. Petersburg, Russian Federation, 197022
Spain
Hospital Clinic
Barcelona, Spain, 08036
Hospital Santa Creu I Sant Pau
Barcelona, Spain, 08025
Hospital Universitario Germans Trias I Pujol
Barcelona, Spain
Hospital Universitario Del Salamanca
Salamanca, Spain, 37007
Hospital Clinico San Carlos
Madrid, Spain, 28048
Hospital Universitario De La Princesa
Madrid, Spain, 28006
Hospital La Paz, Madrid
Madrid, Spain, 28046
Hospital Ramon Y Cajal
Madrid, Spain, 28034
Hospital Son Llatzer
Palma de Mallorca, Spain, 07198
Hospital de Leon
Leon, Spain, 24071
Hospital Universitario La Fe
Valencia, Spain, 46009
Sweden
Sahlgrenska University Hospital
Goteborg, Sweden, S-413 45
Lund Universtiy Hospital
Lund, Sweden, 22185
University Hospital MAS
Malmo, Sweden, S-205 02
Huddinge University Hospital
Stockholm, Sweden, 14186
Uppsala University Hospital
Uppsala, Sweden, S-751 85
United Kingdom
Royal Bournemouth General Hospital
Bournemouth, United Kingdom, BH7 7DW
Royal Cornwall Hospital
Truro, United Kingdom, TR1 3LJ
St. Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Christie Hospital
Manchester, United Kingdom, M20 4BX
Norfolk and Norwich University Hospital
Norwich, United Kingdom, NR4 7UY
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
Kings College Hospital NHS Trust
London, United Kingdom

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

CL Beach

Celgene Corporation

Responsible Party:	Pharmion Corporation ( Linda Zimmerman )
Study ID Numbers:	AZA PH GL 2003 CL 001
Study First Received:	October 31, 2003
Last Updated:	October 8, 2009
ClinicalTrials.gov Identifier:	NCT00071799 History of Changes
Health Authority:	United States: Food and Drug Administration