Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00528983
Recruitment Status : Completed
First Posted : September 14, 2007
Last Update Posted : December 6, 2016
Information provided by (Responsible Party):
Celgene Corporation

Brief Summary:
The purpose of this study is to determine whether a tablet form of azacitidine that taken by mouth is safe. This Phase I study will also look at different doses and different treatment schedules in order to better understand the effects (positive and negative) of oral azacitidine on the body and on the disease MDS, AML and CMML.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes (MDS) Chronic Myelomonocytic Leukemia (CMML) Acute Myelogenous Leukemia (AML) Drug: Subcutaneous (SC) Azacitidine Drug: Oral Azacitidine Phase 1

Detailed Description:

Optional Extension Phase (OEP) to the AZA PH US 2007 CL 005 study which allows subjects who continue to receive oral azacitidine and have stable disease or are demonstrating clinical benefit as assessed by the Investigator, and have consented to participate, may enter the OEP of this study (at their current doses) at the start of their next cycle.

Subjects who are entering the OEP should be discontinued from Part 1 or Part 2 protocol prescribed therapy in the AZA PH US 2007 CL 005 study.

Subjects may continue to receive oral azacitidine in the OEP until they meet the criteria for study discontinuation or oral azacitidine becomes commercially available. Subjects discontinuing from the OEP will have an OEP discontinuation visit 28 days after the last dose of study drug or at study withdrawal.

Primary Objective of OEP is to evaluate long term safety of oral azacitidine.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 133 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myelogenous Leukemia (AML).
Study Start Date : September 2007
Actual Primary Completion Date : July 2013
Actual Study Completion Date : April 2016

Arm Intervention/treatment
Experimental: Subcutaneous (SC) Azacitidine and Oral Azacitidine
Cycle 1 subjects receive SC Azacitidine for first 7 days of 28 day cycle. For Cycle 2 and beyond subjects receive Oral Azacitidine (experimental) for first 7 days of 28 day cycle.
Drug: Subcutaneous (SC) Azacitidine
75 mg/day for first 7 days of 28 day cycle for 1 cycle only.
Other Name: Vidaza

Drug: Oral Azacitidine
Cycle 2 and beyond starting dose of 120 mg/day for first 7 days of 28 day cycle. Dose will escalate in increments of 60 mg. Following evaluation dose escalation will occur in 120 mg increments until maximum tolerated dose (MTD) is reached.
Other Name: CC-486

Experimental: Oral Azacitidine
Subjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.
Drug: Oral Azacitidine
Starting dose for 14 day-QD treatment schedule will be 300 mg/day. Starting dose for 14 day-BID, 21 day-QD, 21 day-BID treatment schedules will be 100 mg, 200mg, 300mg. Dose will escalate in increments of 100 mg until MTD is reached.
Other Name: CC-486

Primary Outcome Measures :
  1. Safety evaluation as measured by monitoring AEs, dose limiting toxicities, scheduled lab assessments, vital sign measurements, ECGs, & physical exams for study duration. Adverse changes in physical signs/symptoms will be graded according to CTC AE V.3.0. [ Time Frame: 60 months ]
  2. Maximum-tolerated dose [ Time Frame: 60 months ]
  3. Pharmacodynamic blood and bone marrow samples will be collected and evaluated. [ Time Frame: 60 months ]

Secondary Outcome Measures :
  1. Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria. [ Time Frame: 60 months ]
  2. Biologically active dose based on safety, PK and PD data. [ Time Frame: 60 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 18 years or older.
  • Diagnosis of low or Int-1 risk MDS
  • Low platelet count, and/or low hemoglobin, and/or RBC transfusion-dependent and/or platelet transfusion-dependent
  • ECOG Performance status 0-2
  • Standard safety inclusion for serum creatinine, AST, ALT, bilirubin.
  • Serum bicarbonate greater than or equal to 20 mEq/L.
  • Use of acceptable birth control.
  • Signed, written informed consent.

Exclusion Criteria:

  • Diagnosis of acute PML.
  • Previous or concurrent malignancy.
  • Prior treatment with azacitidine or other demethylating agents.
  • Treatment with any anticancer therapy or investigational drugs within 21 days.
  • Hypersensitivity to azacitidine or mannitol.
  • Presence of GI disease.
  • Active, uncontrolled infection.
  • Known Human Immunodeficiency Virus (HIV) or Hepatitis C, or known active viral Hepatitis B.
  • Breastfeeding or Pregnant females;
  • Presence of serious illness, medical condition, or other medical history which would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
  • Current congestive heart failure (NY Heart Association Class III-IV), unstable angina or angina requiring surgical or medical intervention within 6 months, myocardial infarct within 6 months, or uncontrolled cardiac arrhythmia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00528983

United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0277
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Indiana
Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46219
United States, Kansas
Kansas University Medical Center
Westwood, Kansas, United States, 66205
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231-1000
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City VA Medical Center University of Kansas Medical Center
Kansas City, Missouri, United States, 64128
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
New York Oncology Hematology P.C.
Albany, New York, United States, 12206
United States, North Carolina
Institute for Translational Oncology Research IRB
Greenville, North Carolina, United States, 29605
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology Cancer Care
Austin, Texas, United States, 78731
MD Anderson Cancer Center
Houston, Texas, United States, 77030
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-4417
Yakima Valley Memorial Hospital/ North Star Lodge
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Celgene Corporation
Study Director: Barry Skikne, M.D., FACP; FCP (SA) Celgene Corporation

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Celgene Corporation Identifier: NCT00528983     History of Changes
Other Study ID Numbers: AZA PH US 2007 CL005
First Posted: September 14, 2007    Key Record Dates
Last Update Posted: December 6, 2016
Last Verified: December 2016

Keywords provided by Celgene Corporation:
Myelodysplastic Syndromes MDS
Acute Myelogenous Leukemia AML
Chronic Myelomonocytic Leukemia CMML

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Juvenile
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors