Acute Myelogenous Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML), Myelodysplastic Syndromes (MDS)
Conditions
Keywords
Myelodysplastic Syndromes MDS, Acute Myelogenous Leukemia AML, Chronic Myelomonocytic Leukemia CMML
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.
Interventions
DRUGSubcutaneous (SC) Azacitidine
75 mg/day for first 7 days of 28 day cycle for 1 cycle only.
DRUGOral 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.
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum-tolerated dose | 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 |
| Pharmacodynamic blood and bone marrow samples will be collected and evaluated. | 60 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed