A Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
I. To determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of
flavopiridol administered as a 30 minute loading dose followed by a 4-hour infusion once
weekly for 4 consecutive weeks every 6 weeks.
II. To determine the safety and feasibility of performing dose escalation to 80 mg/m2 (30
mg/m2 30-minute IV bolus followed by 50 mg/m2 4-hour IV infusion) beginning dose 2 in
patients who do not experience severe tumor lysis requiring hemodialysis during dose 1.
III. To determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol
administered in this schedule.
I. To determine the complete response (CR) and overall response rate (CR + PR) of
flavopiridol in patients with previously-treated CLL administered as a 30 minute loading
dose followed by a 4 hour infusion once weekly for 4 consecutive weeks every 6 weeks.
OUTLINE: This is a dose-escalation study.
Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour
infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in
the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. After the MTD is determined, 12 additional
patients are accrued and treated as above at the recommended phase II dose.
After completion of study treatment, patients are followed at 2 months and then every 3
months for 2 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of flavopiridol determined by dose-limiting toxicities graded assessed utilizing the NCI Common Toxicity Criteria 2.0
Ohio State University
United States: Food and Drug Administration
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