Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

In this study, we are seeking to target the leukemia microenvironment to overcome disease
resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the
bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic
chemotherapy. In this study, we seek to maximize blockage of the SDF-1/CXCR4 axis through
the following:

1. Addition of G-CSF, which down regulates SDF-1 expression and acts synergistically with
plerixafor in stem cell mobilization

2. Intravenous instead of subcutaneous dosing of plerixafor to improve kinetics of
administration.

3. Dose escalation of plerixafor and twice daily dosing to maintain maximum CXCR4
blockade.

Inclusion Criteria:

1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following:

- Primary refractory disease following no more than 2 cycles of induction
chemotherapy

- First relapse with no prior unsuccessful salvage chemotherapy

2. Age between 18 and 70 years old

3. ECOG performance status ≤ 3

4. Adequate organ function defined as:

- Calculated creatinine clearance ≥ 50 ml/min

- AST, ALT, total bilirubin ≤ 2 x ULN except when in the opinion of treating
physician is due to direct involvement of leukemia (eg. hepatic infiltration or
biliary obstruction due to leukemia)

- Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram

5. 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 or urine 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 medically
approved contraception method during and for 3 months after the treatment period

6. Able to provide signed informed consent prior to registration on study

Exclusion Criteria:

1. Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)

2. Peripheral blood blast count ≥ 20 x 103 /mm3

3. Active CNS involvement with leukemia

4. Previous treatment with MEC or other regimen containing both mitoxantrone and
etoposide

5. Pregnant or nursing

6. Received any other investigational agent or cytotoxic chemotherapy (excluding
hydroxyurea) within the preceding 2 weeks

7. Received colony stimulating factors filgrastim or sargramostim within 1 week or
pegfilgrastim within 2 weeks of study

8. Severe concurrent illness that would limit compliance with study requirements