Phase I study of GTI-2040, a ribonucleotide reductase antisense, with high dose cytarabine in patients with relapsed/refractory acute myeloid leukemia.

Abstract

We hypothesized that GTI-2040, a 20-mer oligonucleotide complementary to the R2 subunit mRNA of ribonucleotide reductase, combined with high dose cytarabine (HiDAC) would result in enhanced cytotoxicity by favoring Ara-CTP DNA incorporation. In a phase I dose escalation trial, adults (≥ 60 years) with refractory or relapsed acute myeloid leukemia (AML) received daily HiDAC plus infusional GTI-2040. Using a novel assay, evidence of intracellular drug accumulation and target R2 down-regulation was observed. GTI-2040/HiDAC can be administered safely. However, with no complete remissions observed, alternative doses and schedules may need to be investigated to achieve clinical activity in older patients with AML.

• Authors: Rebecca B Klisovic, William Blum, Zhongfa Liu, Zhiliang Xie, Cheryl Kefauver, Lenguyen Huynh, James A Zwiebel, Steven M Devine, John C Byrd, Michael R Grever, Kenneth K Chan, Guido Marcucci
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 55 Issue 6 Pg. 1332-6 (Jun 2014) ISSN: 1029-2403 [Electronic] United States
• PMID: 24015841 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antimetabolites, Antineoplastic
• Oligodeoxyribonucleotides
• Cytarabine
• GTI2040

Topics

• Aged
• Antimetabolites, Antineoplastic (administration & dosage, therapeutic use)
• Cytarabine (administration & dosage, therapeutic use)
• Female
• Humans
• Leukemia, Myeloid, Acute (diagnosis, pathology, therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Oligodeoxyribonucleotides (administration & dosage, adverse effects, pharmacokinetics)