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

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

doi:10.2217/fon-2020-0044

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

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

Leukemia

Research output: Contribution to journal › Review article › peer-review

50 Scopus citations

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: NCT0254528.

Original language	English (US)
Pages (from-to)	807-815
Number of pages	9
Journal	Future Oncology
Volume	16
Issue number	13
DOIs	https://doi.org/10.2217/fon-2020-0044
State	Published - May 2020

Keywords

AML
MDM2
MIRROS
acute myeloid leukemia
cytarabine
idasanutlin
p53
refractory
relapsed
trial in progress

ASJC Scopus subject areas

Oncology
Cancer Research

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10.2217/fon-2020-0044

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Montesinos, P., Beckermann, B. M., Catalani, O., Esteve, J., Gamel, K., Konopleva, M. Y., Martinelli, G., Monnet, A., Papayannidis, C., Park, A., Récher, C., Rodríguez-Veiga, R., Röllig, C., Vey, N., Wei, A. H., Yoon, S. S., & Fenaux, P. (2020). MIRROS: A randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia. Future Oncology, 16(13), 807-815. https://doi.org/10.2217/fon-2020-0044

Montesinos, P, Beckermann, BM, Catalani, O, Esteve, J, Gamel, K, Konopleva, MY, Martinelli, G, Monnet, A, Papayannidis, C, Park, A, Récher, C, Rodríguez-Veiga, R, Röllig, C, Vey, N, Wei, AH, Yoon, SS & Fenaux, P 2020, 'MIRROS: A randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia', Future Oncology, vol. 16, no. 13, pp. 807-815. https://doi.org/10.2217/fon-2020-0044

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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: NCT0254528.",

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T2 - A randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia

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AU - Beckermann, Benjamin M.

AU - Catalani, Olivier

AU - Esteve, Jordi

AU - Gamel, Katia

AU - Konopleva, Marina Y.

AU - Martinelli, Giovanni

AU - Monnet, Annabelle

AU - Papayannidis, Cristina

AU - Park, Aaron

AU - Récher, Christian

AU - Rodríguez-Veiga, Rebeca

AU - Röllig, Christoph

AU - Vey, Norbert

AU - Wei, Andrew H.

AU - Yoon, Sung Soo

AU - Fenaux, Pierre

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N2 - 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: NCT0254528.

AB - 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: NCT0254528.

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

Abstract

Keywords

ASJC Scopus subject areas

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