scholarly journals Omacetaxine Mepesuccinate

2020 ◽  
Author(s):  
Keyword(s):  
Omacetaxine Mepesuccinate

scholarly journals Pharmacokinetic study of omacetaxine mepesuccinate administered subcutaneously to patients with advanced solid and hematologic tumors

2012 ◽  
Vol 71 (1) ◽  
pp. 35-41 ◽  
Author(s):  
John Nemunaitis ◽  
Alain Mita ◽  
Joe Stephenson ◽  
Monica M. Mita ◽  
John Sarantopoulos ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Omacetaxine Mepesuccinate

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

Blood ◽  
2012 ◽  
Vol 120 (13) ◽  
pp. 2573-2580 ◽  
Author(s):  
Jorge Cortes ◽  
Jeff H. Lipton ◽  
Delphine Rea ◽  
Raghunadharao Digumarti ◽  
Charles Chuah ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Confidence Limit ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Phase 2 ◽  
Lower Confidence Limit ◽  
Hematologic Response ◽  
Lower Confidence ◽  
Omacetaxine Mepesuccinate ◽  
T315i Mutation

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.

Omacetaxine mepesuccinate in chronic-phase chronic myeloid leukemia (CML) in patients resistant, intolerant, or both to two or more tyrosine-kinase inhibitors (TKIs).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6596-6596
Author(s):  
Luke Paul Akard ◽  
Hagop Kantarjian ◽  
Franck E. Nicolini ◽  
Meir Wetzler ◽  
Jeffrey Howard Lipton ◽  
...  
Keyword(s):  
Disease Progression ◽  
Median Duration ◽  
Chronic Phase ◽  
Small Sample ◽  
Clinical Activity ◽  
Phase 2 ◽  
Tumor Cell Death ◽  
Open Label ◽  
Omacetaxine Mepesuccinate ◽  
Pharmaceutical Industries

6596 Background: Omacetaxine mepesuccinate (“omacetaxine”) is a first-in-class, reversible, transient inhibitor of protein elongation that facilitates tumor cell death without depending on BCR-ABL signaling. Clinical activity was shown in two phase 2, open-label, multicenter studies of patients with treatment-resistant CML who had failed at least prior imatinib, many of whom were also resistant to or intolerant of dasatinib and/or nilotinib. Methods: A subset of data from the phase 2 studies included patients in chronic phase who were resistant/intolerant to ≥2 approved TKIs. Omacetaxine 1.25 mg/m2 was given subcutaneously twice daily: ≤14 consecutive days/28-day cycle for induction, ≤7 days/cycle as maintenance. Patients had never achieved or lost response to ≥2 TKIs (R group), were intolerant of ≥2 TKIs (I), or resistant to 1 and intolerant of another (R/I) were evaluated. Results: Of 81 patients (median age, 58 years), 69 were R, 7 I, and 5 R/I. Major cytogenetic response occurred in 13 (19%) in the R group (median duration not reached), 2 (29%) I (median duration 7.4 months), and 1 (20%) R/I (duration 17.7 months). For all patients, cycles of exposure and study duration were 7 cycles and 9.1 months (R); 4 cycles, 7.3 months (I); and 2 cycles, 2.3 months (R/I). Median overall survival in months were 33.9 (R), not reached (I), and 25.0 (R/I). Of 66 (81%) patients with treatment-related grade 3/4 adverse events (AEs), the most common were thrombocytopenia in 44 R, 6 I, and 4 R/I patients and neutropenia in 32 R, 4 I, and 1 R/I. Fifteen patients had an AE leading to discontinuation (10 R, 2 I, 3 R/I), primarily disease progression. There were 9 deaths (the most common were disease progression, sepsis), 8 I, 1 R/I; 2 were considered related to treatment (both sepsis). Conclusions: This subset analysis of patients with chronic-phase CML and prior therapy with ≥2 TKIs shows that omacetaxine provides efficacy and tolerability across TKI-R, I, and R/I groups. Interpretation of the I and the R/I group data was limited by small sample sizes. Support: Teva Pharmaceutical Industries Ltd.

Omacetaxine mepesuccinate in chronic myeloid leukemia

2014 ◽  
Vol 15 (16) ◽  
pp. 2397-2405 ◽  
Author(s):  
Omar Al Ustwani ◽  
Elizabeth A Griffiths ◽  
Eunice S Wang ◽  
Meir Wetzler
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Omacetaxine Mepesuccinate

scholarly journals Metabolite profiling of 14C-omacetaxine mepesuccinate in plasma and excreta of cancer patients

Xenobiotica ◽  
2016 ◽  
Vol 46 (12) ◽  
pp. 1122-1132 ◽  
Author(s):  
Cynthia M. Nijenhuis ◽  
Luc Lucas ◽  
Hilde Rosing ◽  
Philmore Robertson ◽  
Edward T. Hellriegel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Metabolite Profiling ◽  
Omacetaxine Mepesuccinate
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