Phase I and Clinical Pharmacokinetic De-Escalation Study of 2'-Deoxycitidine Administered as a Continuous Infusion in Conjunction With a Continuous Infusion of High-Dose ARA-C in Patients With Refractory Acute Myelogenous Leukemia
OBJECTIVES: I. Estimate the lowest dose of deoxycytidine (dC) that can be given as a host
protective agent in conjunction with high dose cytarabine (HD ARA-C) in patients with
refractory acute myelogenous leukemia or other hematologic malignancies. II. Determine the
maximum tolerated dose and dose-limiting toxic effects of HD ARA-C/dC in these patients.
III. Characterize the pharmacokinetics of continuously administered HD ARA-C/dC in these
patients. IV. Characterize, when possible, the pharmacodynamics of HD ARA-C, dC, and their
metabolites in blasts obtained from leukemic patients participating in this trial. V.
Recommend the lowest possible dose of dC that can be given in combination with HD ARA-C in
future phase II trials.
OUTLINE: This is a dose escalation study. Patients receive deoxycytidine IV over 120 hours.
Beginning 12 hours after initiation of deoxycytidine, patients receive high dose cytarabine
IV over 96 hours. Patients achieving complete response receive no further therapy. Patients
achieving partial response or initial complete response and subsequent relapse receive an
additional course of therapy. Cohorts of 3-6 patients receive escalating doses of
deoxycytidine and high dose cytarabine until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose
PROJECTED ACCRUAL: Approximately 24-30 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Steven Grant, MD
Massey Cancer Center
United States: Federal Government
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