The purpose of this research study is to determine if plerixafor can make cells more
sensitive to killing by Cytarabine and Daunorubicin, an anti-cancer drug regimen referred to
as "7+3" that is commonly used in treating acute myeloid leukemia (AML). In this study,
plerixafor is used with treatments Cytarabine and Daunorubicin and with and without
granulocyte-colony stimulating factor (GCSF). Subjects will be monitored to see how well
they tolerate the use of these drugs together and how well they work to treat the leukemia.
The purpose of the study is to find the highest dose of plerixafor and/or recommended phase
2 dose that can be given safely with Cytarabine and Daunorubicin and with and without
granulocyte-colony stimulating factor (GCSF).
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 109/L for patients not enrolled in a G-CSF-containing cohort
2. >25 x 109/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
