A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy
PRIMARY OBJECTIVES:
I. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of
flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in
patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these
patients.
II. Determine the complete response (CR) and overall response rate (CR and partial response)
of patients treated with flavopiridol.
OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over
30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or
unacceptable toxicity. 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. A total
of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo
blood collection at baseline and periodically during study for pharmacokinetic and cytokine
studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by
enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status,
p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70)
overexpression, and single nucleotide polymorphisms are also examined.
After completion of study treatment, patients are followed at 2 months and then every 3
months for 5 years.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy
Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
Yes
Leslie Andritsos
Principal Investigator
Ohio State University Comprehensive Cancer Center
United States: Food and Drug Administration
NCI-2009-00161
NCT00377104
September 2006
Name | Location |
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Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | Columbus, Ohio 43210-1240 |