Phase II Study of Decitabine in Acute Myeloid Leukemia
I. Determine the rate of complete remission (CR) in patients with previously untreated acute
myeloid leukemia treated with decitabine.
I. Determine the rate of overall survival at 1 year in patients treated with this drug.
II. Determine the overall response rate (CR, incomplete CR, and partial remission) in
patients treated with this drug.
III. Correlate the biological activity of decitabine with clinical endpoints and maximum
concentration of plasma decitabine.
IV. Correlate intracellular concentration of decitabine with global DNA methylation, other
biological endpoints, and clinical response.
Patients receive decitabine IV over 1 hour on days 1-10. Treatment repeats every 28 days in
the absence of disease progression or unacceptable toxicity.
Patients undergo bone marrow aspiration and blood sample collection periodically for
pharmacological and correlative studies. Samples are analyzed for gene expression,
methylation of gene promoters, fetal hemoglobin (HgF), DNMT1 protein expression, maximum
concentration of plasma decitabine, and global DNA methylation. Samples are analyzed by
RT-PCR, Bio-COBRA, matrix-assisted laser desorption ionization time-of-flight mass
spectrometry, SDS-PAGE (polyacrylamide gel electrophoresis), immunoblotting, and LC-MS/MS.
After completion of study treatment, patients are followed for at least 30 days.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of complete remission
Assessment of clinical response will be made according to International Working Group criteria. The major criteria for judging response will include physical examination and examination of blood and bone marrow. For the primary endpoint, all enrolled patients will be analyzed together (regardless of age).
Every 4 weeks, assessed up to 30 days after completion of treatment
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|