Phase I Study of a Pharmacologically Derived Hybrid Bolus-Infusion Schedule of Flavopiridol (NSC 649890, IND 46,211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias
I. Determine the toxicities of escalating doses of flavopiridol administered by "hybrid"
bolus-infusion schedule and given in timed sequence with cytarabine and mitoxantrone
hydrochloride in patients with refractory or relapsed acute leukemia.
II. Determine the incidence of clinical response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of flavopiridol. Patients receive flavopiridol IV
over 30 minutes on days 1, 2, and 3.
Patients receive cytarabine IV continuously over 72 hours beginning on day 6 and
mitoxantrone hydrochloride IV over 60-120 minutes on day 9. Treatment repeats every 35-63
days 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 1 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Serum and bone marrow samples are collected at baseline, during, and after completion of
treatment for future studies. Flavopiridol levels are measured at baseline and on days 1-3
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose determined by dose-limiting toxicities graded according to NCI-CTC version 3.0
Up to 63 days
Johns Hopkins University
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|