The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)

This study is currently recruiting participants.
Verified April 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01566695
First received: March 27, 2012
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk myelodysplastic syndromes (MDS).


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Oral Azacitidine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due to IPSS Lower-risk Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Red blood cell (RBC) transfusion independence [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Red blood cell (RBC) transfusion independence


Secondary Outcome Measures:
  • Number of patients alive [ Time Frame: Up to 60 months ] [ Designated as safety issue: Yes ]
    Number of patients alive

  • Hematological improvement-platelet response (HI-P) [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Hematological improvement-platelet response (HI-P)

  • Duration of RBC transfusion independence [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Duration of RBC transfusion independence

  • Time to RBC transfusion independence [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Time to RBC transfusion independence

  • Progression to acute myeloid leukemia (AML) [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Progression to acute myeloid leukemia (AML)

  • Time to AML progression [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Time to AML progression

  • Hematological improvement-erythroid response (HI-E) [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Hematological improvement-erythroid response (HI-E)

  • Platelet-transfusion independence [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Platelet-transfusion independence

  • Duration of platelet transfusion independence [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Duration of platelet transfusion independence

  • Time to platelet transfusion independence [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Time to platelet transfusion independence

  • Hematologic response [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Hematologic response

  • Clinically significant bleeding events [ Time Frame: Up to 60 months ] [ Designated as safety issue: Yes ]
    Clinically significant bleeding events

  • Number of subjects with adverse events [ Time Frame: Up to 60 months ] [ Designated as safety issue: Yes ]
    Number of subjects with adverse events

  • Health-related quality-of-life [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Health-related quality-of-life

  • Healthcare resource utilization [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Healthcare resource utilization


Estimated Enrollment: 386
Study Start Date: April 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Azacitidine
Arm 1: Oral azacitidine 300mg daily + best supportive care (First 21 days of each 28-day cycle)
Drug: Oral Azacitidine
300mg daily, First 21 days of each 28-day cycle
Placebo Comparator: Placebo
Arm 2: Placebo plus best supportive care (First 21 days of each 28-day cycle)
Drug: Placebo
Placebo, First 21 days of each 28-day cycle

  Eligibility

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

Inclusion Criteria:

  • 18 years or older
  • Have a documented diagnosis of MDS
  • Anemia that requires red blood cell transfusions
  • Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Must agree to follow pregnancy precautions as required by protocol.
  • Must be willing to consent to two or more bone marrow aspirate procedures to be completed during study.

Exclusion Criteria:

  • Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
  • Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide
  • Prior allogeneic or autologous stem cell transplant
  • Eligible for allogenic or autologous stem cell transplant
  • History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect
  • Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)
  • Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization
  • Ongoing adverse events from previous treatment, regardless of the time period
  • Concurrent use of iron-chelating agents, (except for subjects on a stable dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS)
  • Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system is allowed)
  • Significant active cardiac disease within the previous 6 months
  • Uncontrolled systemic fungal, bacterial, or viral infection
  • Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
  • Abnormal coagulation parameters
  • Abnormal liver function test results
  • Abnormal kidney function test results
  • Known or suspected hypersensitivity to azacitidine or mannitol
  • Any significant medical condition, laboratory abnormality, or psychiatric illness
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01566695

Contacts
Contact: Associate Director, Clinical Trial Disclosure 1-888-260-1599 ClinicalTrialDisclosure@celgene.com

  Hide Study Locations
Locations
United States, California
Alta Bates Summit Comprehensive Cancer Center Recruiting
Berkeley, California, United States, 94704
Tower Hematology Oncology Medical Group Recruiting
Beverly Hills, California, United States, 90211
California Cancer Associates for Research & Excellence (cCARE) Recruiting
Fresno, California, United States, 93720
Marin Specialty Care Recruiting
Greenbrae, California, United States, 94904
UCSD Medical Center Thorton Hospital Recruiting
La Jolla, California, United States, 92093
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
United States, Louisiana
East Jefferson General Hospital C/O Cancer Care of Louisiana Recruiting
Metairie, Louisiana, United States, 70006
United States, Massachusetts
University of Massachusetts Worcester Recruiting
Worcester, Massachusetts, United States, 01655
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, Mississippi
Jackson Oncology Associates, PLLC Recruiting
Jackson, Mississippi, United States, 39202
United States, Missouri
Saint Luke's Cancer Institute Recruiting
Kansas City, Missouri, United States, 64111
Kansas City VA Medical Center Recruiting
Kansas City, Missouri, United States, 64128
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
United States, New York
Weill Cornell Medical College - New York-Presbyterian Hospital Recruiting
New York, New York, United States, 10021
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
United States, North Carolina
Carolinas Healthcare System, Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Eastern Institute of Medical Sciences Recruiting
Greenville, North Carolina, United States, 27834
United States, Ohio
University Hospitals, Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
United States, Oregon
Kaiser Permanente Northwest Recruiting
Portland, Oregon, United States, 97227
United States, Pennsylvania
Western Pennsylvania Cancer Institute, c/o Western Pennsylvania Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Brooke Army Medical Center Recruiting
Ft. Sam Houston, Texas, United States, 78234
The University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Millennium Oncology Recruiting
Houston, Texas, United States, 77090
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Hospital Recruiting
Seattle, Washington, United States, 98109
Australia, New South Wales
Royal Prince Albert Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Haematology and Oncology Clinics of Australia Recruiting
Brisbane, Queensland, Australia, 4064
Australia, Victoria
The Northern Hospital Recruiting
Epping, Victoria, Australia, 3076
Cabrina Hospital Malvern Recruiting
Malvern, Victoria, Australia, 3144
Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Peninsula Health Recruiting
Frankston, Victoria, Australia, 3199
Belgium
Grand Hôpital de Charleroi Recruiting
Charleroi, Hainaut, Belgium, 6000
Algemeen Ziekenhuis Sint-Jan Recruiting
Brugge, West-Vlaanderen, Belgium, 8000
AZ Klina Recruiting
Brasschaat, Belgium, 2930
UZ Leuven Recruiting
Leuven, Belgium, 3000
Brazil
Instituto Nacional de Cancer - INCA Not yet recruiting
Rio de Janeiro, RJ, Brazil, 20230-130
Hospital Clinicas de porto Aegre Not yet recruiting
Porto Alegre, RS, Brazil, 90035-903
Hospital Israelita Albert Einstein Not yet recruiting
Sao Paulo, SP, Brazil, 05651-901
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Juravinski Hospital and Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V 1C3
Princess Margaret Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Sunnybrook Health Science Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Hopital Du Sacre-Coeur de Montreal Recruiting
Montréal, Quebec, Canada, H4J 1C5
Czech Republic
Fakultni nemocnice Brno Recruiting
Brno, Jihormoravsky Kraj, Czech Republic, 625 00
Vseobecna fakultni nemocnice v Praze Recruiting
Prague, Czech Republic, 128 00
Ustav hematologie a krevni transfuze Recruiting
Praha, Czech Republic, 128 20
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8000
Odense University Hospital Recruiting
Odense, Denmark, 5000
Roskilde Hospital Recruiting
Roskilde, Denmark, 4000
Finland
Helsinki University Central Hospital Recruiting
Helsinki, Finland, 00 290
Turku University Hospital Recruiting
Turku, Finland, 20520
France
Hopital Saint Louis Recruiting
Bobigny, France, 93000
Hopital Claude Huriez Recruiting
Lille, France, 59037
Institut Paoli Calmettes Recruiting
Marseilles, France, 13009
Hotel-Dieu Recruiting
Nantes, France, 44093
Centre Hospitalier Lyon Sud Recruiting
Pierre Bénite, France, 69495
Hopital Pontchaillou Recruiting
Rennes Cedex 9, France, 35033
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Hopital Civil Recruiting
Strasbourg, France, 67091
Hôpital Purpan Recruiting
Toulouse Cedex 9, France, 31059
Germany
Universitatsklinkum Carl Gustav Carus Recruiting
Dresden, Germany, 1307
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf Recruiting
Dresden, Germany, 1307
Universitätsklinikum Düsseldorf Recruiting
Duesseldorf, Germany, 40225
Marien Hospital Recruiting
Düsseldorf, Germany, 40479
Asklepios Klinik St. Georg Recruiting
Hamburg, Germany, 20099
Universitatsklinikum Schleswig Holstein Recruiting
Kiel, Germany, 24116
Universitätsklinikum Leipzig Recruiting
Leipzig, Germany, 4103
TU München - Klinikum rechts der Isar Recruiting
München, Germany, 81675
Universitaetsklinikum Tuebingen Recruiting
Tuebingen, Germany, 72076
Universitätslinikum Ulm Recruiting
Ulm, Germany, 89081
Israel
Rambam Medical Center Recruiting
Haifa, Israel, 31096
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Italy
Azienda Ospedaliera S. Antonio e Biagio Recruiting
Alessandria, Italy, 15121
Policlinico S. Orsola Malpighi Recruiting
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria Careggi Recruiting
Florence, Italy, 50134
Azienda USL Le/1-Presidio ospedaliero "V. Fazzi" di Lezzo Recruiting
Lecce, Italy, 73100
Ospedale Maggiore Policlinico di Milano Recruiting
Milan, Italy, 20122
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello Recruiting
Palermo, Italy, 90146
Azienda Ospedaliera Bianchi Melacrino Morelli Recruiting
Reggio Calabria, Italy, 89100
Centro di Riferimento Oncologico della Basilicata Recruiting
Rionero in Vulture, Italy, 85028
Azienda Policlinico Umberto I Recruiting
Rome, Italy, 00161
Policlinico Univeritario A. Gemelli Recruiting
Rome, Italy, 00168
Fondazione PTV Policlinico Tor Vergata Recruiting
Rome, Italy, 00133
Universita Degli Studi di Torino Recruiting
Torino, Italy, 10126
Azienda Ospedaliero Universitaria di Udine Recruiting
Udine, Italy, 33100
Ospedale dell'Angelo di Mestre Recruiting
Venezia Mestre, Italy, 30174
Mexico
Hospital Universitario de la UANL "Dr. Jose Eleuterio Gonzalez" Recruiting
Monterrey, Nuevo Leon, Mexico, 64460
Hospital Angeles Lomas Recruiting
Huixquilucan, Mexico, 52763
Avix Investigatcion Clinica Sociedad Civil Recruiting
Monterrey Nuevo Leon, Mexico, 64710
Netherlands
VU Medisch Centrum Recruiting
Amsterdam, Netherlands, 1081 HV
Universitair Medisch Centrum Groningen Recruiting
Groningen, Netherlands, 9713 GZ
UMC St. Radboud Recruiting
Nijmegen, Netherlands, 6500 HB
Erasums MC Recruiting
Rotterdam, Netherlands, 3000 CA
Norway
Forde sentralsjukehus Recruiting
Førde, Norway, N-6807
Oslo University Hospital, Rikshospitalet HF Recruiting
Oslo, Norway, N-0027
Poland
Uniwersyteckie Centrium Kliniczne Recruiting
Gdansk, Poland, 80952
SP ZOZ Szpital Uniwersytecki w Krakowie Recruiting
Krakow, Poland, 31-501
Portugal
Centro Hospital e Universitário de Coimbra Recruiting
Coimbra, Portugal, 3000 075
Instituto Portugues de Oncologia de Lisboz Recruiting
Lisboa, Portugal, 1090 023
Centro Hospitalar de Lisboa central - Hospital de Santo António dos Capuchos Recruiting
Lisboa, Portugal, 1150-314
Instituo Porugues de Oncologia do Porto Recruiting
Porto, Portugal, 4200 072
Spain
Hospital Universitario Germans Trias I Pujol Recruiting
Badalona, Spain, 08910
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Hospital de La Santa Creu i Sa Recruiting
Barcelona, Spain, 8041
Hospital General Universitario Gregorio Marañon Recruiting
Madrid, Spain, 28009
Hospital Univ Ramon y Cajal Recruiting
Madrid, Spain, 28034
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Hospital Universitario Virgen de la Victoria Recruiting
Malaga, Spain, 29010
Hospital Central de Asturias Recruiting
Oviedo, Spain, 33006
Hospital Clínico Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Hospital Universitario Araba Recruiting
Vitoria-Gastiez, Álava, Spain, 1009
Sweden
Sahlgrenska Universitetssjukhuset Recruiting
Goeteberg, Sweden, 41345
University Hospital in Lund Recruiting
Lund, Sweden, 22185
Karolinska University Hosptal,Huddinge Recruiting
Stockholm, Sweden, 14186
United Kingdom
Aberdeen Royal Infirmary Recruiting
Aberdeen, United Kingdom, AB25 2ZN
Bristol Royal Infirmary Recruiting
Bristol, United Kingdom, BS2 8ED
University Hospital of Wales Recruiting
Cardiff, Wells, United Kingdom, CF14 4XW
Northwick Park Hospital Recruiting
Harrow, United Kingdom, HA1 3UJ
Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 5WW
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom, L7 8XP
Guy's and St Thomas' Hospital Recruiting
London, United Kingdom, SE1 9RT
Barts Health NHS Trust, St. Bartholomew's Hospital Recruiting
London, United Kingdom, EC1A 7BE
Manchester Royal Infirmary Recruiting
Manchester, United Kingdom, M13 9WL
Nottingham City Hospital- Dept of Haematology Recruiting
Nottingham, United Kingdom, NG5 1PB
Churchill Hospital Recruiting
Oxford, United Kingdom, OX3 7LE
The Royal Wolverhampton Hospitals NHS Trust Recruiting
Wolverhampton, West Midlands, United Kingdom, WV10 0QP
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Barry Skikne, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01566695     History of Changes
Other Study ID Numbers: AZA-MDS-003, 2012-002471-34
Study First Received: March 27, 2012
Last Updated: April 4, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
Denmark: Danish Health and Medicines Authority
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Lithuania: State Medicine Control Agency - Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Poland : Office of Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Thrombocytopenia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Blood Platelet Disorders
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014