RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combining UCN-01 with fludarabine in treating patients who have relapsed or refractory chronic lymphocytic leukemia or lymphocytic lymphoma.
OBJECTIVES: * Determine the overall response rate in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma treated with UCN-01 and fludarabine. * Assess the molecular changes in CLL cells in peripheral blood in patients treated with this regimen. * Determine the progression-free and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter, dose-escalation study of UCN-01. Patients receive UCN-01 IV over 3 hours on day 1 and fludarabine IV over 30-60 minutes on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 18-46 additional patients receive UCN-01 and fludarabine as above at the recommended phase II dose. PROJECTED ACCRUAL: A total of 12 patients will be accrued for the phase I portion of this study within 6 months. A total of 18-46 patients will be accrued for the phase II portion of this study within 9-23 months.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
Princess Margaret Hospital at University Health Network
Toronto, Ontario, Canada
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