Cytarabine, Idarubicin, Liposome-encapsulated Daunorubicin-Cytarabine or Decitabine in Treating Older Patients With Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the rate of complete remission and mortality at 90 days in the entire cohort
of older patients (>= 60 years) with newly diagnosed acute myeloid leukemia (AML) who receive
clinicogenetic risk-stratified therapy allocation.

SECONDARY OBJECTIVES:

I. To determine the rate of complete remission and mortality at 90 days in subsets of older
patients who receive intensive and low-intensity chemotherapy.

II. To assess the impact of baseline functional status (measured by geriatric assessment) on
the rate of complete remission and mortality at 90 days in older patients, who receive
clinicogenetic risk-stratified therapy allocation.

III. To evaluate the influence of baseline functional status on the quality of life, grades 3
and 4 toxicities (Common Terminology Criteria for Adverse Events [CTCAE] version 4.03 grades)
and neurocognitive status at baseline and at 90 days in older patients.

IV. To determine the symptom burden at diagnosis and 10, 30 and 90 days following initiation
of chemotherapy.

V. To determine proportion of patients with impairments detected by geriatric assessment.

OUTLINE: Patients are assigned to 1 or 2 groups based on cytogenetic and geriatric
assessment-based risk stratification.

GROUP I:

INTENSIVE INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and
idarubicin over 10-15 minutes on days 1-3, or liposome-encapsulated daunorubicin-cytarabine
IV over 90 minutes on days 1, 3 and 5. Treatment continues for 1 course in the absence of
disease progression or unacceptable toxicity.

INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over
1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4
courses in the absence of disease progression or unacceptable toxicity. Patients treated with
liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated
daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks
for 2 courses in the absence of disease progression or unacceptable toxicity.

GROUP II:

LOW-INTENSITY INDUCTION: Patients receive decitabine IV over 1-3 hours on days 1-10.
Treatment repeats every 4 weeks for 1-4 courses in the absence of disease progression or
unacceptable toxicity.

LOW-INTENSITY CONSOLIDATION: Patients who achieve complete remission, receive decitabine IV
over 1-3 hours on days 1-5. Treatment repeats every 4 weeks for 6 or more courses in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 2 years.

Inclusion Criteria:

- A new diagnosis of de novo, secondary or treatment-related AML

- Karnofsky Performance Status >= 60%

- Subjects must be able and willingly give signed informed consent

Exclusion Criteria:

- Acute promyelocytic leukemia (APL); patients with brief exposure to all-trans retinoic
acid (ATRA), arsenic trioxide (ATO) or similar product for suspected APL, who later
turn out not to have APL, are eligible for the study

- Relapsed or refractory AML, who require salvage therapy

- Prior exposure to decitabine or azacitidine will be an exclusion criterion for the use
of decitabine or azacitidine alone

- Patients, who require urgent initiation of chemotherapy (other than debulking agent
such as hydroxyurea or cyclophosphamide) due to leukemia-related emergencies such as
leukostasis, or disseminated intravascular coagulopathy; patients will not be excluded
solely based on prior use of debulking agent; prior or current use of leukapheresis
will be allowed

- Uncontrolled serious infection at the time of enrollment; infections are considered
controlled if appropriate therapy has been instituted and, at the time of enrollment,
patients do not have signs of infection progression; progression of infection is
defined as hemodynamic instability attributable to sepsis, new symptoms, worsening
physical signs or radiographic findings attributable to infection; persisting fever
without other signs or symptoms will not be interpreted as progressing infection

- Uncontrolled clinically significant arrhythmia, myocardial ischemia or congestive
heart failure within the past 2 weeks, that is considered by the treating physician as
a contraindication for initiation of chemotherapy; discussion with the principal
investigator is encouraged if further clarification is required

- Ejection fraction < 45% will be an exclusion criteria for intensive chemotherapy; such
patients may receive low intensity therapy

- Clinically significant kidney (e.g. glomerular filtration rate [GFR] =< 45ml/minute or
creatinine of >= 2 mg/dl) or liver dysfunction (e.g. aspartate aminotransferase
[AST]/alanine aminotransferase (ALT) and/or bilirubin >= 2 times upper limit of normal
[ULN]) at the time of enrollment that may prevent from safely using chemotherapy; such
patients may be allowed to receive low-intensity chemotherapy; patients with elevated
bilirubin secondary to Gilbert syndrome will not be excluded; discussion with the
principal investigator is encouraged if further clarification is required

- Any other condition that may not allow safe use of chemotherapy based on the clinical
judgment of the treating oncologist