期刊
FUTURE ONCOLOGY
卷 15, 期 28, 页码 3197-3208出版社
FUTURE MEDICINE LTD
DOI: 10.2217/fon-2019-0201
关键词
acute myeloid leukemia; CPI-613; cytarabine; Devimistat; mitoxantrone; pyruvate dehydrogenase; tricarboxcylic acid; alpha-ketoglutarate dehydrogenase
类别
Devimistat (CPI-613 R (R)) is an intravenously administered, novel lipoate analog that inhibits two key tricarboxcylic acid (TCA) cycle enzymes, pyruvate dehydrogenase (PDH) and a-ketoglutarate dehydrogenase complexes (KGDH). These complexes control TCA cycle entry of glucose and glutamine-derived carbons, respectively. Acute myeloid leukemia (AML) cells upregulate the TCA cycle in response to DNA damaging agents and treatment with devimistat increases sensitivity to them. A Phase I study of devimistat in combination with cytarabine and mitoxantrone produced a complete remission rate of 50% in patients with relapsed or refractory AML. In the combined Phase I/II experience, older patients with R/R AML treated with 2000 mg/m(2) of devimistat had a 52% complete remission/complete remission with incomplete hematologic recovery rate and a median survival of 12.4 months. This report outlines the rationale and design of the ARMADA 2000 study, a Phase III clinical trial of devimistat in combination with high dose cytarabine and mitoxantrone compared with high dose cytarabine and mitoxantrone alone for older patients (>= 60 years of age) with relapsed or refractory AML.
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