Literature DB >> 24015841

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

Rebecca B Klisovic1, 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.   

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.

Entities:  

Keywords:  Acute myeloid leukemia; GTI-2040; antisense therapy; phase I study; ribonucleotide reductase

Mesh：

Substances：

Year:  2013        PMID： 24015841      PMCID： PMC4298748          DOI： 10.3109/10428194.2013.838764

Source DB:  PubMed          Journal:  Leuk Lymphoma        ISSN： 1026-8022


  28 in total

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Review 4.  Oligonucleotide therapeutics for hematologic disorders.

Authors:  N Agarwal; A M Gewirtz
Journal:  Biochim Biophys Acta       Date:  1999-12-10

Review 5.  Nucleoside analogues: mechanisms of drug resistance and reversal strategies.

Authors:  C M Galmarini; J R Mackey; C Dumontet
Journal:  Leukemia       Date:  2001-06       Impact factor: 11.528

6.  Thymidylate synthase (TS) and ribonucleotide reductase (RNR) may be involved in acquired resistance to 5-fluorouracil (5-FU) in human cancer xenografts in vivo.

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Journal:  Eur J Cancer       Date:  2001-09       Impact factor: 9.162

Review 7.  Treatment of relapsed and refractory acute myelogenous leukemia.

Authors:  E H Estey
Journal:  Leukemia       Date:  2000-03       Impact factor: 11.528

8.  Molecular and biochemical mechanisms of fludarabine and cladribine resistance in a human promyelocytic cell line.

Authors:  E Månsson; T Spasokoukotskaja; J Sällström; S Eriksson; F Albertioni
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9.  Different pathways of 5-fluorouracil metabolism after continuous venous or bolus injection in patients with colon carcinoma: possible predictive value of thymidylate synthetase mRNA and ribonucleotide reductase for 5-fluorouracil sensitivity.

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Journal:  Anticancer Res       Date:  2002 Nov-Dec       Impact factor: 2.480

10.  Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia.

Authors:  Guido Marcucci; John C Byrd; Guowei Dai; Marko I Klisovic; Peter J Kourlas; Donn C Young; Spero R Cataland; Diane B Fisher; David Lucas; Kenneth K Chan; Pierluigi Porcu; Zhong-Pin Lin; Sherif F Farag; Stanley R Frankel; James A Zwiebel; Eric H Kraut; Stanley P Balcerzak; Clara D Bloomfield; Michael R Grever; Michael A Caligiuri
Journal:  Blood       Date:  2002-08-22       Impact factor: 22.113
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  1 in total

1.  A phase I pharmacodynamic study of GTI-2040, an antisense oligonucleotide against ribonuclotide reductase, in acute leukemias: a California Cancer Consortium study.

Authors:  Mark H Kirschbaum; Paul Frankel; Timothy W Synold; Zhiliang Xie; Yun Yen; Leslie Popplewell; Robert Chen; Omar Aljitawi; Joseph M Tuscano; Kenneth K Chan; Edward M Newman
Journal:  Leuk Lymphoma       Date:  2016-02-19
  1 in total

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