MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia.

Abstract

Patients with refractory or relapsed acute myeloid leukemia (R/R AML) have a poor prognosis, with a high unmet medical need. Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53. By preventing the p53-MDM2 interaction, idasanutlin allows for p53 activation, particularly in patients with TP53 wild-type (WT) status. MIRROS (NCT02545283) is a randomized Phase III trial evaluating idasanutlin + cytarabine versus placebo + cytarabine in R/R AML. The primary end point is overall survival in the TP53-WT population. Secondary end points include complete remission rate (cycle 1), overall remission rate (cycle 1) and event-free survival in the TP53-WT population. MIRROS has an innovative design that integrates a stringent interim analysis for futility; continuation criteria were met in mid-2017 and accrual is ongoing. Trial registration number: NCT02545283.

• Authors: Pau Montesinos, Benjamin M Beckermann, Olivier Catalani, Jordi Esteve, Katia Gamel, Marina Y Konopleva, Giovanni Martinelli, Annabelle Monnet, Cristina Papayannidis, Aaron Park, Christian Récher, Rebeca Rodríguez-Veiga, Christoph Röllig, Norbert Vey, Andrew H Wei, Sung-Soo Yoon, Pierre Fenaux
• Journal: Future oncology (London, England) (Future Oncol) Vol. 16 Issue 13 Pg. 807-815 (May 2020) ISSN: 1744-8301 [Electronic] England
• PMID: 32167393 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Pyrrolidines
• RG7388
• Tumor Suppressor Protein p53
• para-Aminobenzoates
• Cytarabine
• Proto-Oncogene Proteins c-mdm2

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cytarabine (therapeutic use)
• Female
• Humans
• Leukemia, Myeloid, Acute (drug therapy, metabolism)
• Male
• Proto-Oncogene Proteins c-mdm2 (metabolism)
• Pyrrolidines (therapeutic use)
• Remission Induction
• Tumor Suppressor Protein p53 (metabolism)
• para-Aminobenzoates (therapeutic use)