Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To assess the safety (at 3 months) and feasibility of administering daunorubicin
hydrochloride (daunorubicin) as continuous infusion under the proposed treatment regimen.

SECONDARY OBJECTIVES:

I. To assess the safety (at 6 months) of administering daunorubicin as continuous infusion
under the proposed treatment regimen.

II. To assess treatment outcomes (including complete remission [CR] and complete remission
with incomplete recovery [CRi]) in patients with acute myeloid leukemia (AML) under the
proposed treatment regimen.

III. To compare the concordance between magnetic resonance imaging (MRI) and echocardiogram
(ECHO) in identifying cardiac toxicity, ie a reduction in left ventricular ejection fraction
(LVEF) of >= 10% and ejection fraction (EF) =< 50% compared to baseline LVEF.

OUTLINE:

INDUCTION: Patients receive cytarabine intravenously (IV) continuously over 24 hours on days
1-7 and daunorubicin hydrochloride IV continuously over 24 hours on days 1-3 in the absence
of disease progression or unacceptable toxicity. Patients then undergo bone marrow aspirate
and biopsy on day 14. Patients with bone marrow cellularity >= 10% and > 5% leukemic blasts,
may receive a second induction of cytarabine IV continuously over 24 hours on days 1-5 and
daunorubicin hydrochloride IV continuously over 24 hours on days 1-2 in the absence of
disease progression or unacceptable toxicity.

CONSOLIDATION: Patients achieving remission receive cytarabine IV over 3 hours every 12 hours
on days 1, 3, and 5. Treatment repeats every 28 days for up to 3 courses in the absence of
disease progression or unacceptable toxicity. Patients with core-binding factor (CBF) AML may
receive 4 courses of therapy.

After completion of study treatment, patients are followed up for a minimum of 30 days, at 3
and 6 months, and then every 3 months thereafter.

Inclusion Criteria:

- Patients must have morphologically confirmed newly diagnosed acute myelogenous
leukemia (AML) with blood or bone marrow disease; patients with only extramedullary
disease in the absence of bone marrow or blood involvement are eligible; note: this
protocol uses World Health Organization (WHO) diagnostic criteria for AML; patients
with acute promyelocytic leukemia (APL, French-American-British Classification [FAB],
M3) or blastic transformation of chronic myelogenous leukemia (CML) are not eligible

- Eastern Cooperative Oncology Group (ECOG) performance status 0-3

- Patients with ECHO EF >= 45% within 28 days prior to registration

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Ability to understand and the willingness to sign an Institutional Review Board
(IRB)-approved informed consent document

Exclusion Criteria:

- Patients who have received prior induction chemotherapy for AML or myelodysplastic
syndrome (MDS); temporary prior measures such as apheresis or hydroxyurea are allowed;
patients who have received a limited and short-term exposure of ATRA (all trans
retinoic acid) while AML-M3 (acute promyelocytic leukemia) was being ruled out, and
which has been discontinued, will be eligible

- Patients receiving any other investigational agents

- Patients with prolonged corrected QT (QTc) interval (> 500 msec) determined by
electrocardiogram (EKG) within 28 days prior to registration

- Patients not suitable for cardiac MRI; contraindications include:

- Intracranial metal, pacemakers, defibrillators, functioning neurostimulator
devices, or other implanted electronic devices

- Ferromagnetic cerebral aneurysm clips, or other intraorbital/intracranial metal

- Allergy to gadolinium or other severe drug allergies

- Claustrophobia

- Congestive heart failure (New York Heart Association [NYHA] class III or IV)

- Significant valvular disease, or significant pulmonary disease requiring
supplemental oxygen therapy

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to daunorubicin or cytarabine

- Patients with documented central nervous system (CNS) involvement

- Patients who are known to be human immunodeficiency virus (HIV) positive (+) may be
eligible providing they meet all of the following additional criteria within 28 days
prior to registration:

- CD4 cells >= 500/mm^3

- Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on
combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on
cART

- No zidovudine or stavudine as part of cART Patients who are HIV+ and do not meet
all of these criteria are not eligible for this study

- Patients with other uncontrolled intercurrent illness or psychiatric illness/social
situations that would limit compliance with study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued
prior to beginning treatment