Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
This pilot clinical trial studies potential genetic markers which might be used to predict which patients with acute myeloid leukemia or myelodysplastic syndromes respond to decitabine. This study will contribute to the efforts to find effective and less toxic therapies to provide durable remissions in a significant proportion of elderly AML patients.
Leukemia, Myeloid, Acute
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Genomic Predictors of Decitabine Response in AML/MDS|
- Correlation of patient specific mutations with overall response rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]Best response after 4 treatment cycles as assessed according to International Working Group (IWG) criteria; bone marrow for gene sequencing will be collected at baseline; mutations will be correlated with overall response and their respective 95% confidence intervals will be provided.
- Compare efficacy of a10-day decitabine per cycle regimen to a 5-day regimen (historical controls) [ Time Frame: 4 months (4 treatment cycles) ] [ Designated as safety issue: No ]Efficacy defined as complete response (complete response [CR]/CR with incomplete blood count recovery [CRi]) and overall response (CR+CRi + partial response [PR]); response assessed according to IWG criteria;
- Bone marrow mutation expression profile and change in profile during decitabine treatment [ Time Frame: 60 days ] [ Designated as safety issue: No ]Samples collected at baseline and after 10, 28 and 56 days of therapy; compare the rate of mutation clearance and lowest mutation frequencies between the patients who achieve a CR/CRi after 4 cycles and those who do not
- Steady-state plasma decitabine concentration [ Time Frame: Day 4 ] [ Designated as safety issue: No ]The steady-state plasma decitabine concentration on day 4 +/- 1 will be measured and correlated with clinical overall response.
- Decrease in bone marrow methylcytosine [ Time Frame: Baseline and Day 10 ] [ Designated as safety issue: No ]Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline and its association with both steady-state serum drug levels and response will be assessed using 2-way ANOVA for repeated measurement data
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||January 2019|
|Estimated Primary Completion Date:||April 2018 (Final data collection date for primary outcome measure)|
Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Other Name: 5-aza-dCyd, 5AZA, DAC, Dacogen, deoxyazacytidine, dezocitidine
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687400
|Contact: John Welch, M.D., Ph.D.||email@example.com|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|St. Louis, Missouri, United States, 63110|
|Contact: John Welch, M.D., Ph.D. 314-362-2626|
|Sub-Investigator: Timothy Ley, M.D.|
|Sub-Investigator: Jeffrey Klco, M.D., Ph.D.|
|Principal Investigator:||Welch John, M.D., Ph.D.||Washington University School of Medicine|