Related Experiment Video
Updated: Dec 26, 2025
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute
Pau Montesinos1,2, Benjamin M Beckermann3, Olivier Catalani3
1Departamento de Hematologia, Hospital Universitari i Politècnic La Fe, València, Spain.
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.
Insights
Idasanutlin shows promise for patients with refractory or relapsed acute myeloid leukemia (R/R AML). This trial investigates idasanutlin plus cytarabine versus placebo plus cytarabine in R/R AML.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- Refractory or relapsed acute myeloid leukemia (R/R AML) presents a significant unmet medical need due to poor prognosis.
- Idasanutlin targets MDM2, a protein that inhibits the tumor suppressor p53, thereby enabling p53 activation.
- p53 activation by idasanutlin is particularly relevant in patients with wild-type TP53 (TP53-WT).
Purpose of the Study:
- To evaluate the efficacy and safety of idasanutlin in combination with cytarabine compared to placebo with cytarabine in patients with R/R AML.
- To assess overall survival as the primary endpoint in the TP53-WT population.
- To determine secondary endpoints including remission rates and event-free survival in the TP53-WT population.
Main Methods:
- MIRROS is a Phase III randomized clinical trial (NCT02545283).
- The trial compares idasanutlin + cytarabine to placebo + cytarabine in R/R AML patients.
- An interim analysis for futility was integrated into the trial design.
Main Results:
- Continuation criteria were met in mid-2017, indicating the trial's progression.
- Patient accrual is ongoing, suggesting continued interest and enrollment.
- Specific efficacy or safety results are not yet available as the trial is ongoing.
Conclusions:
- The MIRROS trial is investigating a novel therapeutic approach for R/R AML.
- Idasanutlin's mechanism of action offers a potential new treatment strategy for TP53-WT AML.
- The trial's design, including an interim futility analysis, aims for efficient evaluation of idasanutlin's potential benefit.
