Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

• 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 serum decitabine concentration [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  The steady-state serum 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

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
• Myelodysplastic Syndromes

Inclusion Criteria:

ONE OF THE FOLLOWING:

• Patient must have non-M3 AML and be >= 60 years of age OR
• Non-M3 AML with relapsed disease OR
• Symptomatic MDS with one of the following:
• Symptomatic anemia with either hemoglobin < 10.0 g/dL or requiring red blood cell (RBC) transfusion
• Thrombocytopenia with a history of two or more platelet counts < 50,000/mcL or a significant hemorrhage requiring platelet transfusions
• Neutropenia with two or more absolute neutrophil count (ANC) < 1,000/mcL

ALL OF THE FOLLOWING:

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patient must have > 10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics
• Peripheral white blood cell count =< 50,000/mcl
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Serum creatinine =< 2.0 x ULN
• Patient must have undergone =< 2 cycles of prior hypomethylating agent (decitabine or azacitidine)
• Patient must be enrolled in Human Research Protections Office (HRPO) # 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Malignancies")
• Patient myst be >= 18 years of age
• Patient must be able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document

Exclusion Criteria:

• Patient must not be pregnant or nursing
• Patient must not have known central nervous system (CNS) leukemia
• Patient must not have a history of positive human immunodeficiency virus (HIV) serology
• Patient must not have a history of positive hepatitis C serology
• Patient must not have undergone prior allogeneic stem cell transplant
• Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, ongoing or active graft-versus-host disease (GVHD), congestive heart failure of New York Heart Association (NYHA) class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
• Patient must not have had radiation therapy within 14 days of enrollment