GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia
|Acute Undifferentiated Leukemia Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Blastic Phase Chronic Myelogenous Leukemia de Novo Myelodysplastic Syndromes Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia||Drug: GTI-2040 Procedure: pharmacological study Procedure: laboratory biomarker analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I and Pharmacodynamic Study of GTI-2040 (NSC 722929, IND 67368) in Acute Leukemias|
- 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) [ Time Frame: 28 days ]
- Change in dCTP levels in PBMC and bone marrow by Real-Time PCR [ Time Frame: Days 1, 4, 15, and 19 of course 1 ]
- Objective tumor response [ Time Frame: Up to 3 years ]
- Overall survival [ Time Frame: Up to 3 years ]
- Time to failure [ Time Frame: Up to 3 years ]
- Duration of response [ Time Frame: Up to 3 years ]
- Change in expression levels of R1, R2, and p53R2 mRNA in PBMC by Real-Time PCR [ Time Frame: Day 1, 4, 15, and 19 of course 1 ]
- Change in intracellular levels of GTI-2040 by ELISA [ Time Frame: Day 1, 4, 15, and 19 of course 1 ]
- Incidence of grade 3 or higher toxicity assessed by CTCAE v3.0 [ Time Frame: Up to 3 years ]
|Study Start Date:||March 2007|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive GTI-2040 IV continuously on days 1-4 and 15-18.
Given IVProcedure: pharmacological study
Other Name: pharmacological studiesProcedure: laboratory biomarker analysis
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00459212
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|Principal Investigator:||Mark Kirschbaum||City of Hope Medical Center|