An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia
Autor: | Jeff P. Sharman, Michael Boxer, Michael J. Hawkins, Jing Hu, Steve Abella, Leonard M. Klein, Kathryn S. Kolibaba, Chris A. Yasenchak, Meihua Wu |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Male
medicine.medical_specialty Indazoles Clinical Trials and Observations Chronic lymphocytic leukemia Immunology Phases of clinical research Neutropenia Biochemistry Gastroenterology Disease-Free Survival Internal medicine medicine Humans Syk Kinase Adverse effect Protein Kinase Inhibitors Aged Aged 80 and over business.industry Intracellular Signaling Peptides and Proteins Cell Biology Hematology Middle Aged Protein-Tyrosine Kinases medicine.disease Leukemia Lymphocytic Chronic B-Cell Lymphoma Pyrazines Cohort Female Refractory Chronic Lymphocytic Leukemia business Febrile neutropenia |
Popis: | Small-molecule inhibitors of kinases involved in B-cell receptor signaling are an important advance in managing lymphoid malignancies. Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. This multicenter, phase 2 study enrolled subjects with relapsed or refractory chronic lymphocytic leukemia (CLL; n = 41) or non-Hodgkin lymphoma (n = 145). Participants received 800 mg entospletinib twice daily. We report efficacy outcomes in the CLL cohort (n = 41) and safety outcomes in all cohorts (N = 186). The primary end point was a progression-free survival (PFS) rate at 24 weeks in subjects with CLL. The PFS rate at 24 weeks was 70.1% (95% confidence interval [CI], 51.3%-82.7%); median PFS was 13.8 months (95% CI, 7.7 months to not reached). The objective response rate was 61.0% (95% CI, 44.5%-75.8%), including 3 subjects (7.3%) who achieved nodal response with persistent lymphocytosis. Fifty-four subjects (29.0%) had serious adverse events (SAEs). The most common treatment-emergent SAEs included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia. Common grade 3/4 laboratory abnormalities included neutropenia (14.5%) and reversible alanine aminotransferase/aspartate aminotransferase elevations (13.4%). Entospletinib demonstrates clinical activity in subjects with relapsed or refractory CLL with acceptable toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01799889. |
Databáze: | OpenAIRE |
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