Phase ia/ii, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies
DeAngelo, D J ; Spencer, A ; Bhalla, K N ; Prince, H M ; Fischer, T ; Kindler, T ; Giles, F J ; Scott, J W ; Parker, K ; Liu, A ... show 4 more
DeAngelo, D J
Spencer, A
Bhalla, K N
Prince, H M
Fischer, T
Kindler, T
Giles, F J
Scott, J W
Parker, K
Liu, A
Repository DOI
Publication Date
2013-02-06
Keywords
panobinostat, histone deacetylase, myelofibrosis, hodgkin lymphoma, myelodysplastic disorders, myeloma, histone deacetylase inhibitors, t-cell lymphoma, hypoxia-inducible factor-1-alpha, refractory multiple-myeloma, international-working-group, response criteria, hydroxamic acid, lbh589, acetylation, vorinostat
Type
Article
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Citation
DeAngelo, D J; Spencer, A; Bhalla, K N; Prince, H M; Fischer, T; Kindler, T; Giles, F J; Scott, J W; Parker, K; Liu, A; Woo, M; Atadja, P; Mishra, K K; Ottmann, O G (2013). Phase ia/ii, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia 27 (8), 1628-1636
Abstract
Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and myeloma). In patients with leukemia and myeloid disorders, 60 mg was the MTD for weekly as well as biweekly panobinostat. In patients with lymphoma and myeloma, 40 mg was the recommended dose for phase II evaluation (formal MTD not determined) of weekly panobinostat, and 60 mg was the MTD for biweekly panobinostat. Overall, panobinostat-related grade 3-4 adverse events included thrombocytopenia (41.5%), fatigue (21%) and neutropenia (21%). Single-agent activity was observed in several indications, including Hodgkin lymphoma and myelofibrosis. This phase Ia/II study provided a broad analysis of the safety profile and efficacy of single-agent panobinostat in patients with hematologic malignancies.
Funder
Publisher
Springer Nature
Publisher DOI
10.1038/leu.2013.38
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland