Activity of the mTOR inhibitor sirolimus and HDAC inhibitor vorinostat in heavily pretreated refractory Hodgkin lymphoma patients.

8508 Background: Preclinical models suggested synergistic antineoplastic activity of HDAC and mTOR inhibitors in Hodgkin lymphoma by reducing the activity of AKT, mTOR and HDAC. Methods: We designed a phase I study to determine the safety of the mTOR inhibitor sirolimus (1mg-5mg PO daily q 28 days) and HDAC inhibitor vorinostat (100mg-400mg PO daily q 28 days) in advanced cancers with an expansion cohort at the recommended phase 2 dose (RP2D) of sirolimus 4mg and vorinostat 300mg for patients with refractory classical Hodgkin lymphoma. The expansion cohort included optional pre- and post-treatment tumor biopsies, peripheral blood mononuclear cells (PBMCs), plasma/serum collections for pharmacodynamic (PD) and pharmacokinetic (PK) endpoints. Upon identification of R2PD patients were allowed to be treated and registered off label if protocol spots were not available. Results: A total of 28 patients (men, n=15; women, n=13), median age 34 years, median of 6 prior therapies (including autologous SCT [n=23], a...