UCN-01 and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

OBJECTIVES:

Primary

- Define the maximum tolerated dose and recommended phase II dose of UCN-01 administered
after perifosine in patients with relapsed or refractory acute leukemia, chronic
myelogenous leukemia, or high risk myelodysplastic disorders.

Secondary

- Evaluate the safety and toxicity of UCN-01 administered after perifosine in these
patients.

- Evaluate the safety and toxicity of perifosine administered after UCN-01 in these
patients.

- Document responses in patients treated with this regimen.

- Observe the pharmacokinetics of both perifosine and UCN-01 when administered in
combination.

- Study the pharmacodynamics of perifosine alone, UCN-01 alone, and in combination in
leukemic blast cells.

OUTLINE: This is a multicenter, dose-escalation study of UCN-01. The first patients enrolled
in the study are assigned to group 1. Once the maximum tolerated dose (MTD) is determined in
group 1, subsequent patients are enrolled in group 2.

- Group 1: Patients receive a loading dose of oral perifosine every 6 hours on day 1
followed by a maintenance dose once daily on days 2-28 of course 1 and then once daily
on days 1-28 in all subsequent courses. Patients also receive UCN-01 IV over 3 hours on
day 4.

Cohorts of 3-6 patients receive escalating doses of UCN-01 until the MTD is determined. The
MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting
toxicity.

- Group 2: Patients receive UCN-01 IV over 3 hours on day 1 at the MTD determined in
group I. Patients also receive oral perifosine as a loading dose every 6 hours on day 4
followed by a maintenance dose once daily on days 5-28 of course 1 and then once daily
on days 1-28 in all subsequent courses.

In both groups, treatment repeats every 28 days for ≥ 2 courses in the absence of disease
progression or unacceptable toxicity. Patients who achieve a complete remission (CR) or a CR
with incomplete hematologic recovery receive 4 additional courses beyond documentation of
CR. Patients who achieve a partial remission or hematologic improvement may continue
treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days and then periodically
thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.