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
| Autor: | Timothy S. Pardee, Marc Buyse, Bayard L. Powell, Sanjeev Luther, Jorge E. Cortes |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Sulfides 03 medical and health sciences 0302 clinical medicine Refractory High dose cytarabine Older patients Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Prospective Studies Aged Salvage Therapy Mitoxantrone business.industry Cytarabine International Agencies Myeloid leukemia General Medicine Middle Aged Prognosis Pyruvate dehydrogenase complex Survival Rate Clinical trial Leukemia Myeloid Acute 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Female Caprylates Neoplasm Recurrence Local business Follow-Up Studies medicine.drug |
| Zdroj: | Future Oncology. 15:3197-3208 |
| ISSN: | 1744-8301 1479-6694 |
| Popis: | 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#03504410 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|