Study of ABT-751 in Patients With Refractory Hematologic Malignancies

The current low cure rates in most patients with advanced hematologic cancers indicate the
need to identify new agents that can be incorporated with current therapies to improve
prognosis. The vinca alkaloids are effective broad-spectrum anti-leukemic drugs. Microtubules
are a major structural component of cells. They play a role in cell shape, cellular polarity,
cellular movement, intracellular transport and the segregation of chromosomes during mitosis.
The cellular microtubule dynamics are highly regulated. As cells enter mitosis, the
interphase microtubules disappear and are replaced with a new network of microtubules that
interact with the mitotic spindle. Disruption of these new microtubules leads to cell cycle
arrest. These important and highly labile microtubule arrays comprising the mitotic spindle
are the principal target of oncologic antimitotic compounds. Known antimitotic agents fall
into three classes, the vinca alkaloids (vincristine, vinblastine, and vinorelbine), taxanes
(paclitaxel and docetaxel), and colchicine-site binders. There are no colchicine-site agents
currently approved for cancer chemotherapy. These three classes of compounds have distinct
binding sites on the tubulin subunits. ABT-751 is a novel orally administered antimitotic
agent that binds to the colchicine site on beta-tubulin and inhibits polymerization of
microtubules.

Inclusion Criteria

- Patients with relapsed or refractory acute leukemias (AML, ALL, MDS [RAEB, RAEBT],
CMML in transformation with >/= 10% peripheral blood/bone marrow blasts, CML in blast
crisis), and patients with relapsed/refractory or transformed CLL.

- Signed informed consent indicating that patients are aware of the investigational
nature of this study, and in keeping with the policies of this hospital.

- ECOG performance status
- Serum direct bilirubin serum creatinine
- Age > 16 years - a separate Phase I study is being conducted in the pediatric
population.

Exclusion Criteria

- Any severe, concurrent disease, infection, or co-morbidity that, in the judgment of
the Investigator, would make the patient inappropriate for study entry.

- Pregnant and/or lactating females.

- Those with documented sulfonamide allergy should be excluded from study participation.