Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myelogenous Leukemia
- Conditions
- Myelodysplastic Syndromes (MDS)Chronic Myelomonocytic Leukemia (CMML)Acute Myelogenous Leukemia (AML)
- Interventions
- Registration Number
- NCT00528983
- Lead Sponsor
- Celgene
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 133
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Subcutaneous (SC) Azacitidine and Oral Azacitidine 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. Oral Azacitidine Oral Azacitidine Subjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle. Subcutaneous (SC) Azacitidine and Oral Azacitidine Subcutaneous (SC) 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.
- Primary Outcome Measures
Name Time Method Maximum-tolerated dose 60 months Pharmacodynamic blood and bone marrow samples will be collected and evaluated. 60 months 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. 60 months
- Secondary Outcome Measures
Name Time Method Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria. 60 months Biologically active dose based on safety, PK and PD data. 60 months
Trial Locations
- Locations (18)
Institute for Translational Oncology Research IRB
🇺🇸Greenville, North Carolina, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Central Indiana Cancer Centers
🇺🇸Indianapolis, Indiana, United States
Kansas University Medical Center
🇺🇸Westwood, Kansas, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
New York Oncology Hematology P.C.
🇺🇸Albany, New York, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Yakima Valley Memorial Hospital/ North Star Lodge
🇺🇸Yakima, Washington, United States
HOAST
🇺🇸San Antonio, Texas, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Kansas City VA Medical Center University of Kansas Medical Center
🇺🇸Kansas City, Missouri, United States
Texas Oncology Cancer Care
🇺🇸Austin, Texas, United States