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

作者：Klisovic Rebecca B; Blum William; Liu Zhongfa; Xie Zhiliang; Kefauver Cheryl; Huynh Lenguyen; Zwiebel James A; Devine Steven M; Byrd John C; Grever Michael R; Chan Kenneth K; Marcucci Guido^*

来源：Leukemia and Lymphoma, 2014, 55(6): 1332-1336.

DOI：10.3109/10428194.2013.838764

• Acute myeloid leukemia
• antisense therapy
• phase I study
• GTI-2040
• ribonucleotide reductase

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.

• 出版日期2014-6