Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myelogenous Leukemia
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).
1 other identifier
interventional
133
1 country
18
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2007
Longer than P75 for phase_1
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 11, 2007
CompletedStudy Start
First participant enrolled
September 11, 2007
CompletedFirst Posted
Study publicly available on registry
September 14, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
April 5, 2016
CompletedNovember 8, 2019
November 1, 2019
5.9 years
September 11, 2007
November 6, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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
Maximum-tolerated dose
60 months
Pharmacodynamic blood and bone marrow samples will be collected and evaluated.
60 months
Secondary Outcomes (2)
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
Study Arms (2)
Subcutaneous (SC) Azacitidine and Oral Azacitidine
EXPERIMENTALCycle 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
EXPERIMENTALSubjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.
Interventions
75 mg/day for first 7 days of 28 day cycle for 1 cycle only.
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.
Eligibility Criteria
You may qualify if:
- 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
- Serum bicarbonate greater than or equal to 20 mEq/L.
- Use of acceptable birth control.
- Signed, written informed consent.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (18)
University of Florida
Gainesville, Florida, 32610-0277, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Central Indiana Cancer Centers
Indianapolis, Indiana, 46219, United States
Kansas University Medical Center
Westwood, Kansas, 66205, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21231-1000, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Kansas City VA Medical Center University of Kansas Medical Center
Kansas City, Missouri, 64128, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
New York Oncology Hematology P.C.
Albany, New York, 12206, United States
Institute for Translational Oncology Research IRB
Greenville, North Carolina, 29605, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Texas Oncology Cancer Care
Austin, Texas, 78731, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
HOAST
San Antonio, Texas, 78229, United States
Virginia Oncology Associates
Norfolk, Virginia, 23502, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-4417, United States
Yakima Valley Memorial Hospital/ North Star Lodge
Yakima, Washington, 98902, United States
Related Publications (3)
Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, Laille E, Giordano H, Sakoian S, Jabbour E, Kantarjian H, Skikne B. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011 Jun 20;29(18):2521-7. doi: 10.1200/JCO.2010.34.4226. Epub 2011 May 16.
PMID: 21576646BACKGROUNDGarcia-Manero G, Gore SD, Kambhampati S, Scott B, Tefferi A, Cogle CR, Edenfield WJ, Hetzer J, Kumar K, Laille E, Shi T, MacBeth KJ, Skikne B. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016 Apr;30(4):889-96. doi: 10.1038/leu.2015.265. Epub 2015 Oct 7.
PMID: 26442612BACKGROUNDLaille E, Shi T, Garcia-Manero G, Cogle CR, Gore SD, Hetzer J, Kumar K, Skikne B, MacBeth KJ. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies. PLoS One. 2015 Aug 21;10(8):e0135520. doi: 10.1371/journal.pone.0135520. eCollection 2015.
PMID: 26296092DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Barry Skikne, M.D., FACP; FCP (SA)
Celgene Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 11, 2007
First Posted
September 14, 2007
Study Start
September 11, 2007
Primary Completion
July 31, 2013
Study Completion
April 5, 2016
Last Updated
November 8, 2019
Record last verified: 2019-11