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, Omacetaxine 202 Study Group, Sikander Ailawadhi, Luke Akard, Maria Baer, Michele Baccarani, Robert Emmons, Gabriel Etienne, Agnès Guerci, François Guilhot, Andrzej Hellmann, Françoise Huguet-Rigal, H Jean Khoury, Pierre Laneuville, Philipp Le Coutre, Laurence Legros, Armin Leitner, Frederic Maloisel, David Marin, Tamas Masszi, Purvish Parikh, Candido Rivera, Philippe Rousselot, Thierry Facon, Richard Van Etten, Krzysztof Warzocha, Meir Wetzler, Peter Wiernik, 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, Omacetaxine 202 Study Group, Sikander Ailawadhi, Luke Akard, Maria Baer, Michele Baccarani, Robert Emmons, Gabriel Etienne, Agnès Guerci, François Guilhot, Andrzej Hellmann, Françoise Huguet-Rigal, H Jean Khoury, Pierre Laneuville, Philipp Le Coutre, Laurence Legros, Armin Leitner, Frederic Maloisel, David Marin, Tamas Masszi, Purvish Parikh, Candido Rivera, Philippe Rousselot, Thierry Facon, Richard Van Etten, Krzysztof Warzocha, Meir Wetzler, Peter Wiernik
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/m(2) 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.
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Source: PubMed