Study of Plerixafor Combined 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