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)

NCT ID: NCT01566695

Last Updated: 2025-01-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

216 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-26

Study Completion Date

2023-12-21

Brief Summary

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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).

Detailed Description

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Conditions

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Myelodysplastic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Oral Azacitidine

Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.

Group Type EXPERIMENTAL

Oral Azacitidine

Intervention Type DRUG

300 mg daily, days 1 to 21 of each 28-day treatment cycle

Best Supportiv Care (BSC)

Intervention Type OTHER

BSC included and was not limited to packed RBC (packed red blood cell \[pRBC\] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.

Placebo

Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Identically matching placebo tablets on day 1 to 21 of each 28-day treatment cycle.

Best Supportiv Care (BSC)

Intervention Type OTHER

BSC included and was not limited to packed RBC (packed red blood cell \[pRBC\] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.

Interventions

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Oral Azacitidine

300 mg daily, days 1 to 21 of each 28-day treatment cycle

Intervention Type DRUG

Placebo

Identically matching placebo tablets on day 1 to 21 of each 28-day treatment cycle.

Intervention Type DRUG

Best Supportiv Care (BSC)

BSC included and was not limited to packed RBC (packed red blood cell \[pRBC\] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.

Intervention Type OTHER

Other Intervention Names

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CC-486

Eligibility Criteria

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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.
* Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted

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 (for lenalidomide : unless the last dose received is \>= 8 weeks prior to inclusion into the study).
* 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 medically significant adverse events from previous treatment, regardless of the time period
* Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Alta Bates Comprehensive Cancer Center

Berkeley, California, United States

Site Status

Tower Hematology/Oncology Medical Group and Tower Cancer Research Found

Beverly Hills, California, United States

Site Status

City Of Hope

Duarte, California, United States

Site Status

California Cancer Associates for Research and Excellence cCARE

Escondido, California, United States

Site Status

Marin Oncology Associates

Greenbrae, California, United States

Site Status

UCSD-Thornton Hospital

La Jolla, California, United States

Site Status

University of Southern California Norris Cancer Center

Los Angeles, California, United States

Site Status

Local Institution - 942

New Haven, Connecticut, United States

Site Status

University of Florida Health Cancer Center at Orlando Health

Orlando, Florida, United States

Site Status

Phoebe Cancer Center of Phoebe Putney Memorial Hospital

Albany, Georgia, United States

Site Status

Robert H Lurie Comprehensive Cancer Center NW Univ

Chicago, Illinois, United States

Site Status

University Of Illinois At Chicago

Chicago, Illinois, United States

Site Status

University Of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Loyola University Chicago

Maywood, Illinois, United States

Site Status

University Of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Louisville, J.G. Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Hematology And Oncology Specialists, Llc

Metairie, Louisiana, United States

Site Status

Johns Hopkins Medicine

Baltimore, Maryland, United States

Site Status

UMASS Memorial Hospital

Worcester, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Jackson Oncology Associates PLLC

Jackson, Mississippi, United States

Site Status

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Site Status

Kansas City VA Medical Center University of Kansas Medical Center

Kansas City, Missouri, United States

Site Status

University Of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Weill Cornell Medical College - New York - Presbyterian Hospital

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai Medical Center

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Eastern Institute of Medical Sciences

Greenville, North Carolina, United States

Site Status

University Hospitals of Cleveland Case Medical Center

Cleveland, Ohio, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Local Institution - 917

Portland, Oregon, United States

Site Status

Penn Medicine: University of Pennsylvania Health System

Philadelphia, Pennsylvania, United States

Site Status

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Brooke Army Medical Center Francis Street Medical Center

Fort Sam Houston, Texas, United States

Site Status

Local Institution - 900

Houston, Texas, United States

Site Status

Local Institution - 924

Houston, Texas, United States

Site Status

Millennium Physicians - Oncology

Houston, Texas, United States

Site Status

VA Commonwealth University - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Local Institution - 904

Seattle, Washington, United States

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Waukesha Memorial Hospital

Waukesha, Wisconsin, United States

Site Status

Local Institution - 137

Garran, Australian Capital Territory, Australia

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Local Institution - 129

Adelaide, South Australia, Australia

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Local Institution - 134

Clayton, Victoria, Australia

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Frankston, Victoria, Australia

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Camperdown, , Australia

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Epping, VIC, , Australia

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Fitzroy, , Australia

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Kogarah, , Australia

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Malvern, , Australia

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Milton, Brisbane, , Australia

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Waratah, , Australia

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Woolloongabba, , Australia

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Brasschaat, , Belgium

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Bruges, , Belgium

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Charleroi, , Belgium

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Leuven, , Belgium

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Fortaleza, Ceará, Brazil

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Curitiba, Paraná, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Barrie, Ontario, Canada

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Brno, South Moravian, Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Aarhus, , Denmark

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Odense C, , Denmark

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Roskilde, , Denmark

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Helsinki, , Finland

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Turku, , Finland

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Lille, , France

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Marseille, , France

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Nantes, , France

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Paris, , France

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Pierre-Bénite, , France

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Rennes, , France

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Rouen, , France

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Strasbourg, , France

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Toulouse, , France

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Tours, , France

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Dresden, , Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Düsseldorf, , Germany

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Hamburg, , Germany

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Keil, , Germany

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Leipzig, , Germany

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München, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Heraklion, Irakleio, Greece

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Alexandroupoli, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Pátrai, , Greece

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Tel Aviv, Tel Aviv, Israel

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Haifa, , Israel

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Petah Tikva, , Israel

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Tel Litwinsky, , Israel

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Alessandria, , Italy

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Bari, , Italy

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Bologna, , Italy

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Cagliari, , Italy

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Florence, , Italy

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Lecce, , Italy

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Milan, , Italy

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Novara, , Italy

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Palermo, , Italy

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Pavia, , Italy

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Pisa, , Italy

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Reggio Calabria, , Italy

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Rionero in Vulture, , Italy

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Roma, , Italy

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Roma, , Italy

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Terni, , Italy

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Torino, , Italy

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Torrette Di Ancona, , Italy

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Udine, , Italy

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Venezia - Mestre, , Italy

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Huixquilucan de Degollado, , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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Tlalpan, , Mexico

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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Førde, , Norway

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Oslo, , Norway

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Beja, , Portugal

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Coimbra, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Porto, , Portugal

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Busan, , South Korea

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Daegu, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Local Institution - 626

Badalona (Barcelona), , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Granada, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Oviedo, , Spain

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Salamanca, , Spain

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Seville, , Spain

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Vitoria-Gasteiz, Álava, , Spain

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Gothenburg, , Sweden

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Lund, , Sweden

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Stockholm, , Sweden

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Adana, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Mersin, , Turkey (Türkiye)

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Trabzon, , Turkey (Türkiye)

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Oxford, Oxfordshire, United Kingdom

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Aberdeen, , United Kingdom

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Birmingham, , United Kingdom

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Bristol, , United Kingdom

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Cambridge, , United Kingdom

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Cardiff, , United Kingdom

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Harrow Middlesex, , United Kingdom

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Hull, , United Kingdom

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Leicester, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Local Institution - 684

London, , United Kingdom

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Local Institution - 679

Manchester, , United Kingdom

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Nottingham, , United Kingdom

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Local Institution - 690

Sutton in Ashfield, , United Kingdom

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Local Institution - 680

Wolverhampton, , United Kingdom

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Countries

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United States Australia Belgium Brazil Canada Czechia Denmark Finland France Germany Greece Israel Italy Mexico Netherlands Norway Poland Portugal South Korea Spain Sweden Turkey (Türkiye) United Kingdom

References

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Garcia-Manero G, Almeida A, Giagounidis A, Platzbecker U, Garcia R, Voso MT, Larsen SR, Valcarcel D, Silverman LR, Skikne B, Santini V. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia. BMC Hematol. 2016 May 3;16:12. doi: 10.1186/s12878-016-0049-5. eCollection 2016.

Reference Type BACKGROUND
PMID: 27148452 (View on PubMed)

Garcia-Manero G, Santini V, Almeida A, Platzbecker U, Jonasova A, Silverman LR, Falantes J, Reda G, Buccisano F, Fenaux P, Buckstein R, Diez Campelo M, Larsen S, Valcarcel D, Vyas P, Giai V, Oliva EN, Shortt J, Niederwieser D, Mittelman M, Fianchi L, La Torre I, Zhong J, Laille E, Lopes de Menezes D, Skikne B, Beach CL, Giagounidis A. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes. J Clin Oncol. 2021 May 1;39(13):1426-1436. doi: 10.1200/JCO.20.02619. Epub 2021 Mar 25.

Reference Type DERIVED
PMID: 33764805 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2012-002471-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AZA-MDS-003

Identifier Type: -

Identifier Source: org_study_id

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