A Phase I/II Study of Flavopiridol (NSC 649890, IND 46,211) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Poor-Risk Acute Leukemias
I. To determine the toxicities of escalating doses of flavopiridol administered in a timed
sequence with ara-C and mitoxantrone in adults with refractory or relapsed acute leukemias
or high-risk myelodysplasias (MDS).
II. To determine if flavopiridol administered in a timed sequence with ara-C and
Mitoxantrone will induce clinical responses in adults with refractory or relapsed acute
leukemias or MDS.
III. To determine if flavopiridol is directly cytotoxic to leukemic blasts in vivo.
IV. To determine if flavopiridol can recruit and synchronize residual leukemic blasts to
proliferate in vivo.
OUTLINE: This is a dose-escalation study of flavopiridol. (Phase I closed to accrual
Patients receive flavopiridol IV over 1 hour on days 1-3 and cytarabine IV continuously on
days 6-9 followed by mitoxantrone IV over 30-150 minutes on day 9. Patients achieving a
partial or complete response after the first course of therapy may receive an additional
course of therapy beginning 35 ± 7 days after blood count recovery.
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 at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I closed to accrual
effective 10/24/2003). Once the MTD is reached, additional patients are accrued to receive
flavopiridol at the recommended phase II dose.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (DLT) as assessed by NCI CTC version 2.0
Up to 35 days
Johns Hopkins University
United States: Food and Drug Administration
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