IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)

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 current formulations, the volume of plerixafor required to administer
doses higher than 240 mcg/kg may result in significant discomfort with repeated daily
injections. In this phase I extension study, we seek to test the safety of both higher
doses of plerixafor as well as intravenous dosing to maximize inhibition of the target,
CXCR4.

Inclusion Criteria:

- Acute myeloid leukemia diagnosed according to WHO criteria with one of the following:

- Primary refractory disease following ≥ 1 round of induction chemotherapy

- First relapse or higher

- Age between 18 and 70 years

- ECOG performance status ≤ 2

- Adequate organ function defined as:

- Creatinine ≤ 1.5 x institutional ULN

- AST

- ALT

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

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

- Women of childbearing potential and sexually active males must be willing and able to
use effective contraception while on study

- Able to provide signed informed consent prior to registration on study

Exclusion Criteria:

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

- Peripheral blood blast count ≥ 50 x 103 /mm3

- Active CNS involvement with leukemia

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

- Pregnant or nursing

- Concurrently receiving any other investigational agent

- Received colony stimulating factors filgrastim or sargramostim within 48 hours or
pegfilgrastim within 14 days of study

- Less than 2 weeks from the completion of any previous cytotoxic chemotherapy
(excluding hydroxyurea)

- Severe concurrent illness that would limit compliance with study requirements