Abstract
Devimistat (CPI-613®) is an intravenously administered, novel lipoate analog that inhibits two key tricarboxcylic acid (TCA) cycle enzymes, pyruvate dehydrogenase (PDH) and α-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/m2 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. Clinical trial registration: NCT#0350441.
Original language | English (US) |
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Pages (from-to) | 3197-3208 |
Number of pages | 12 |
Journal | Future Oncology |
Volume | 15 |
Issue number | 28 |
DOIs | |
State | Published - 2019 |
Keywords
- CPI-613
- Devimistat
- acute myeloid leukemia
- cytarabine
- mitoxantrone
- pyruvate dehydrogenase
- tricarboxcylic acid
- α-ketoglutarate dehydrogenase
ASJC Scopus subject areas
- Oncology
- Cancer Research