Disrupting the Bone Marrow Microenvironment With G-CSF in Acute Lymphoblastic Leukemia

In this study, we will combine G-CSF as priming prior to and during the administration of
salvage chemotherapy regimen in ALL. Abundant data suggests that leukemic cells receive key
growth and survival signals from the bone marrow microenvironment. Our preclinical data show
that 4-5 days of G-CSF treatment is associated with a loss of osteoblasts and decreases
expression of key chemokine/ cytokines which support lymphocyte development. The
investigators hypothesize that G-CSF will disrupt the protective effects of the bone marrow
microenvironment and augment the effect of chemotherapy in adults with ALL. This is a pilot
study of G-CSF priming in adult patients with relapsed or refractory ALL to determine the
feasibility and to characterize the effect of G-CSF treatment on the marrow
microenvironment.

Inclusion Criteria:

- Acute lymphoblastic leukemia diagnosed according to WHO criteria (>25% lymphoblasts
in BM) which is relapsed or refractory to therapy. Patients with t(9;22) must be
refractory to BCR-ABL tyrosine kinase inhibitors.

- Age ≥ 18 years

- ECOG performance status ≤ 3.

- Adequate organ function defined as:

- Calculated creatinine clearance ≥ 50 ml/min

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

- 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:

- Previous salvage chemotherapy with ifosfamide and etoposide

- Pregnant or nursing

- Received any other investigational agent or cytotoxic chemotherapy within the
preceding 2 weeks

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

- Severe concurrent illness that would limit compliance with study requirements