A Phase I, Dose Escalation Study of Plerixafor in Combination With Cytarabine and Daunorubicin in Patients With Newly Diagnosed Acute Myeloid Leukemia

Inclusion Criteria:

- Provide signed, dated informed consent prior to any protocol-specific procedures.

- Have a diagnosis of newly diagnosed AML, defined as >20% myeloblasts on the marrow
aspirate or peripheral blood differential, with or without extramedullary
involvement, with confirmatory immunophenotyping or immunocytochemistry (e.g.,
myeloperoxidase), documented within 14 days of enrollment.

- Have Eastern Cooperative Oncology Group (ECOG) performance status (Appendix A) score
of 0, 1, or 2.

- Toxicities from all prior treatments have resolved to baseline or δ Grade 1 prior to
first dose of study drugs.

- Are surgically or biologically sterile or willing to practice acceptable birth
control, as follows: Females of child bearing potential must agree to abstain from
sexual activity or to use a medically approved contraceptive measure/regimen during
and for 3 months after the treatment period. Women of child bearing potential must
have a negative serum pregnancy test at the time of enrollment. Acceptable methods
of birth control include oral contraceptive, intrauterine device (IUD),
transdermal/implanted or injected contraceptives and abstinence.

- Males must agree to abstain from sexual activity or agree to utilize a
medially-approved contraception method during and for 3 months after the treatment
period.

- Have adequate renal and hepatic function, as indicated by the following laboratory
values: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) δ2.5 -
upper limit of normal (ULN); Estimated creatinine clearance (CrCl) of > 50mL/min, as
calculated by the Cockcroft-Gault equation (Appendix F); total bilirubin ≤1.5-ULN
(except in patients with Gilbert Syndrome, in whom direct bilirubin must be
≤1.5-ULN), International Normalized Ratio (INR) ≤1.5 after discontinuation of
anticoagulants.

- Have adequate cardiac function, as measured by left ventricular ejection fraction
(LVEF) ≥40% on echocardiography or multigated acquisition (MUGA) scan or similar
radionuclide angiographic scan.

- Be able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

- Have received previous systemic treatment for leukemia or antecedent hematologic
disorder (AHD), other than hydroxyurea or hematopoietic growth factors. Treatment
with hydroxyurea within 2 weeks of screening is allowed but must be discontinued at
least 24 hours prior to the first dose of study drugs.

- Have received prior treatment with plerixafor, cytarabine, or any anthracycline.

- Have a diagnosis of acute promyelocytic leukemia (APL), French-American-British (FAB)
classification M3 or World Health Organization (WHO) classification of APL with
t(15;17)(q(22;q12), or Bcr-Abl positive leukemia.

- For patients < 50 years of age, have cytogenetics associated with good prognosis
[(t(8;21)q(22;22), t(15;17),inv(16)(p13;q22)]. (Testing for these mutations must be
performed on blood or Bone Marrow prior to study registration.

- Have had a hematopoietic stem cell transplant (HSCT).

- Have an absolute blast count of the following at the time of first dose of
chemotherapy, despite cytoreduction with hydroxyurea or leukapheresis:

1. >50 x 10^9/L for patients not enrolled in a G-CSF-containing cohort

2. >25 x 10^9/L for patients enrolled in a G-CSF-containing cohort

- Have central nervous system (CNS) leukemia (Only patients with suspected CNS leukemia
must undergo lumbar puncture.)

- Have any of the following within the last 12 months: unstable supraventricular
arrhythmia (e.g., hemodynamic instability) or has a pacemaker; Any ventricular
arrhythmia, other than occasional premature ventricular contractions; Congestive
heart failure (controlled or uncontrolled); Myocardial infarction, ischemia, stable
coronary artery disease, or angina; Uncontrolled hypertension; Syncope with either a
known cardiovascular or an unknown etiology.

- Have a pre-existing disorder predisposing the patient to serious or life-threatening
infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding
disorder, or cytopenias).

- Have the need for anticoagulant therapy.

- Have a significant medical or psychiatric disorder that would interfere with consent,
study participation, or follow-up.

- Have an active acute or chronic systemic fungal, bacterial, viral, or other infection
(i.e., exhibiting ongoing signs/symptoms related to the infection [except isolated
fever] and without improvement, despite appropriate antibiotics or other treatment).

- Have severe concurrent diseases (e.g., a history of serious organ dysfunction or
disease) that may place the patient at undue risk to undergo induction therapy per
protocol, or obscure assessments of drug safety.

- Have a diagnosis of prior malignancy unless disease-free for at least 5 years
following therapy with curative intent, with the following exceptions:

1. Patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, if
definitive treatment for the condition has been completed; or

2. Patients with organ-confined prostate cancer with no evidence of recurrent or
progressive disease based on prostate-specific antigen (PSA) values after
treatment with curative intent.

- Have known human immunodeficiency virus (HIV) positivity or evidence of active viral
hepatitis.

- Are pregnant or breastfeeding.

- Are known to have an allergy to any component of the study drug regimen