Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Condition: Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: decitabine
Intervention MeSH terms: Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 114.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This 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.
    

Eligibility criteria:

        Inclusion Criteria:

        All of the following:

          -  Patient must have non-M3 AML or MDS

          -  An adverse risk karyotype defined by:

               -  Complex karyotype by cytogenetics, or

               -  Deletion of all or part of chromosome 5, 7, 12, or 17 defined by FISH or
                  cytogenetics, or

               -  Somatic TP53 mutation

        All of the following:

          1. Patient must have an ECOG performance status ≤ 2.

          2. Patient must have >10% disease burden measured by cytomorphology, flow cytometry, or
             cytogenetics.

          3. Patient must have peripheral white blood cell count < 50,000/mcl.

          4. Patient must have adequate organ function, defined as:

               1. Total bilirubin < 1.5 x ULN

               2. AST/ALT < 2.5 x ULN

               3. Serum creatinine < 2.0 x ULN

          5. Patient must have undergone ≤ 2 cycles of prior hypomethylating agent (decitabine or
             azacitidine).

          6. Patient must be enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of
             Genetic Progression Factors in Hematologic Diseases").

          7. Patient must be > 18 years of age.

          8. Patient must be able to understand and willing to sign an IRB-approved written
             informed consent document.

        Exclusion Criteria:

          -  Patient must not be pregnant or nursing

          -  Patient must not have acute promyelocytic leukemia or t(15;17) observed by FISH.

          -  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

          -  Patient must not have received any chemotherapy within 21 days of enrollment and any
             acute treatment-related toxicities must have returned to baseline. Patients may be
             receiving hydrea at time of enrollment.