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

  Show 130 Study Locations
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