Phase I and Pharmacodynamic Study of GTI-2040 (NSC 722929, IND 67368) in Acute Leukemias
I. Determine the maximum tolerated dose of GTI-2040 in patients with relapsed, refractory,
or high-risk acute leukemia, high-grade myelodysplastic syndromes, or refractory or blastic
phase chronic myelogenous leukemia.
II. Assess the toxicity and efficacy of this drug in these patients. III. Assess plasma and
intracellular pharmacokinetics of this drug in these patients.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive GTI-2040 IV continuously on days 1-4 and 15-18. Treatment repeats every 28
days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 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-limiting toxicity.
Blood samples are collected on days 1, 4, 15, and 19 of course 1 for pharmacokinetic
studies. Samples are analyzed by proteomic assay, dCTP pool measurement, and real-time
polymerase chain reaction for mRNA of RRM2, RRM1, and p53R2.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
City of Hope Medical Center
United States: Food and Drug Administration
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