Guadecitabine With or Without Idarubicin or Cladribine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Condition: Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Cladribine; Guadecitabine; Idarubicin
Intervention description: Given IV; Given SC; Given IV
Intervention MeSH terms: Idarubicin; Cladribine; 2-chloro-3'-deoxyadenosine; Guadecitabine; Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well guadecitabine with or without idarubicin or
      cladribine works in treating older patients with previously untreated acute myeloid leukemia.
      Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for
      cell growth. Drugs used in chemotherapy, such as idarubicin and cladribine, work in different
      ways to stop the growth of cancer cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. It is not yet known whether guadecitabine with
      or without idarubicin or cladribine is more effective in treating older patients with
      previously untreated acute myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated AML patients, except those who have received prior therapy with
             hydroxyurea, single agent chemotherapy (e.g. decitabine), hematopoietic growth
             factors, biological or targeted therapies are allowed

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Sign a written informed consent form

          -  Total bilirubin =< 2 mg/dL

          -  Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic
             transaminase (SGOT) =< 4 x upper limit of normal (ULN)

          -  Creatinine clearance of >= 50 mL/min (estimated by the Cockcroft-Gault [C-G] formula)

          -  Male patients must use an effective contraceptive method during the study and for a
             minimum of 8 weeks after study treatment

          -  Baseline left ventricular ejection fraction (LVEF) >= 40%

        Exclusion Criteria:

          -  Patients with >= New York Heart Association (NYHA) grade 3 heart disease as assessed
             by history and/or physical examination

          -  Patients who received more than one full course of prior hypomethylating agents
             azacitidine or decitabine

          -  Have any other severe concurrent disease, or have a history of serious organ
             dysfunction or disease involving the heart, kidney, liver, or other organ system that
             may place the patient at undue risk to undergo treatment

          -  Patients with a systemic fungal, bacterial, viral, or other infection not controlled
             (defined as exhibiting ongoing signs/symptoms related to the infection and without
             improvement, despite appropriate antibiotics or other treatment)

          -  Pregnant or lactating patients

          -  Any significant concurrent disease, illness, or psychiatric disorder that would
             compromise patient safety or compliance, interfere with consent, study participation,
             follow up, or interpretation of study results

          -  Any concurrent malignancy with the exception of the following: a) patients with
             treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial
             neoplasia, regardless of the disease-free duration, are eligible for this study if
             definitive treatment for the condition has been completed; b) patients with
             organ-confined prostate cancer with no evidence of recurrent or progressive disease
             based on prostate-specific antigen (PSA) values are also eligible for this study if
             hormonal therapy has been initiated or a radical prostatectomy has been performed