Acute Myeloid Leukemia, Leukemia, Myelomonocytic, Chronic, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes
Conditions
Keywords
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Chronic Myelomonocytic Leukemia (CMML)
Brief summary
The purpose of this study is to compare the amount of drug that gets into the bloodstream between different tablets taken by mouth and an injection under the skin.
Interventions
DRUGazacitidine
Arm 1: Cycle 1 (PK Phase) - Subjects will receive a single SC dose of 75 mg/m2 on Days 1 and 15. Single oral doses of a given formulation of azacitidine will be administered in increasing doses on Days 3 and 5, and at doses calculated to deliver 80% and 120% of the SC exposure, up to a maximum dose of 600 mg on Days 17 and 19. Cycles 2 and beyond - (Treatment phase) Oral azacitidine will be administered in a dose calculated to deliver 100% of the SC exposure up to a maximum of 600 mg on days 1 - 7 of a 28 day cycle. Arm 2: All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.
Sponsors
Celgene
Study design
Allocation
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 MDS or CMML * Diagnosis of AML, Multiple myeloma, Hodgkin's or Non-Hodgkin's lymphoma for whom standard curative or palliative measures do not exist or are no longer effective * ECOG Performance Status 0-2 * Use of acceptable birth control * Standard safety inclusion for serum creatinine, AST, ALT, bilirubin * Serum bicarbonate greater than or equal to 20 mEq/L * Platelet count greater than or equal to 25,000/uL * Hemoglobin greater than or equal to 500/uL * Signed informed consent
Exclusion criteria
* Diagnosis of acute promyelocytic leukemia * Treatment with demethylating agents within 21 days prior to Cycle 1, Day 1 * Treatment with any anticancer therapy (standard or investigational) within 21 days prior to Cycle 1, Day 1 or ongoing adverse events from previous treatment * Hypersensitivity to azacitidine or mannitol * Active, uncontrolled infection * Presence of GI disease, malignant tumors or other conditions known to interfere with ADME * Known or active HIV, viral hepatitis B or C * Breastfeeding or pregnant females * Current or uncontrolled cardiac disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To estimate the dose for a given oral formulation that would yield similar exposure [area under the curve (AUC)] to 75 mg/m2 of the subcutaneous formulation. | 1 - 18 months |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine | 1 - 18 months |
| To assess response rates | 1 - 18 months |
| To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation | 1 - 18 months |
| To investigate the pharmacokinetics of oral azacitidine | 1 -18 months |
| To assess the pharmacodynamic effects of oral azacitidine | 1 -18 months |
| To assess RBC transfusion independence | 1 - 18 months |
Countries
United States
Outcome results
None listed