A phase I/II trial of MEC (mitoxantrone, etoposide, cytarabine) in combination with ixazomib for relapsed refractory acute myeloid leukemia

Anjali S. Advani, Brenda Cooper, Valeria Visconte, Paul Elson, Ricky Chan, Jennifer Carew, Wei Wei, Sudipto Mukherjee, Aaron Gerds, Hetty Carraway, Aziz Nazha, Betty Hamilton, Ronald Sobecks, Paolo Caimi, Benjamin Tomlinson, Ehsan Malek, Jane Little, Alexander Miron, John Pink, Jaroslaw MaciejewskiAllison Unger, Matt Kalaycio, Marcos de Lima, Mikkael A. Sekeres

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Purpose: The prognosis of patients with relapsed/refractory thrombocytopenia. Despite a poor risk population, the (R/R) acute myeloid leukemia (AML) remains poor, and novel response rate [complete remission (CR)/CR with incomplete therapies are needed. The proteasome pathway represents a count recovery (CRi)] was encouraging at 53%. Gene-potential therapeutic target. A phase I trial of the second-expression analysis identified two genes, IFI30 (g-interferon generation proteasome inhibitor ixazomib in combination inducible lysosomal thiol reductase) and RORa (retinoic with MEC (mitoxantrone, etoposide, and cytarabine) was orphan receptor A), which were significantly differentially conducted in patients with R/R AML. expressed between responding and resistant patients and Patients and Methods: Dose escalation of ixazomib was could classify CR. performed using a standard 3 3 design. Gene-expression Conclusions: These results are encouraging, but a random-profiling was performed on pretreatment and posttreatment ized trial is needed to address whether the addition of ixazo-bone marrow or blood samples. mib to MEC improves outcome. Gene-expression profiling Results: The maximum tolerated dose of ixazomib in com-also helped us identify predictors of response and potentially bination with MEC was 1.0 mg. The dose limiting toxicity was novel therapeutic targets.

Original languageEnglish (US)
Pages (from-to)4231-4237
Number of pages7
JournalClinical Cancer Research
Volume25
Issue number14
DOIs
StatePublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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