This trial is active, not recruiting.

Conditions myelodysplastic syndromes (mds), chronic myelomonocytic leukemia (cmml), acute myelogenous leukemia (aml)
Treatments subcutaneous (sc) azacitidine, oral azacitidine
Phase phase 1
Sponsor Celgene Corporation
Start date September 2007
End date July 2013
Trial size 133 participants
Trial identifier NCT00528983, AZA PH US 2007 CL005


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
subcutaneous (sc) azacitidine Vidaza
75 mg/day for first 7 days of 28 day cycle for 1 cycle only.
oral azacitidine CC-486
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.
Subjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.
oral azacitidine CC-486
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.

Primary Outcomes

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
Maximum-tolerated dose
time frame: 60 months
Pharmacodynamic blood and bone marrow samples will be collected and evaluated.
time frame: 60 months

Secondary Outcomes

Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria.
time frame: 60 months
Biologically active dose based on safety, PK and PD data.
time frame: 60 months

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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).
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Celgene Corporation.