Devimistat in combination with high dose cytarabine and mitoxantrone compared with high dose cytarabine and mitoxantrone in older patients with relapsed/refractory acute myeloid leukemia: ARMADA 2000 Phase III study

Timothy S. Pardee, Sanjeev Luther, Marc Buyse, Bayard L. Powell, Jorge Cortes

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)3197-3208
Number of pages12
JournalFuture Oncology
Volume15
Issue number28
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • acute myeloid leukemia
  • CPI-613
  • cytarabine
  • Devimistat
  • mitoxantrone
  • pyruvate dehydrogenase
  • tricarboxcylic acid
  • α-ketoglutarate dehydrogenase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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