Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation

Jorge Cortes, Jeff H. Lipton, Delphine Rea, Raghunadharao Digumarti, Charles Chuah, Nisha Nanda, Annie Claude Benichou, Adam R. Craig, Mauricette Michallet, Franck E. Nicolini, Hagop Kantarjian

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors. Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and tyrosine kinase inhibitor failure. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily, days 1-14, every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n - 62) received a median of 7 (range, 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit, 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% lower confidence limit, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation. This study is registered at www.clinicaltrials.gov as NCT00375219.

Original languageEnglish (US)
Pages (from-to)2573-2580
Number of pages8
JournalBlood
Volume120
Issue number13
DOIs
StatePublished - Sep 27 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Cortes, J., Lipton, J. H., Rea, D., Digumarti, R., Chuah, C., Nanda, N., Benichou, A. C., Craig, A. R., Michallet, M., Nicolini, F. E., & Kantarjian, H. (2012). Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood, 120(13), 2573-2580. https://doi.org/10.1182/blood-2012-03-415307