@article{Farhad Ravandi_Iphigenia Koumenis_Anandhi Johri_Martin Tallman_Gail J. Roboz_Stephen Strickland_Guillermo Garcia-Manero_Gautam Borthakur_Kiran Naqvi_Meghan Meyer_Madhu Pudipeddi_Sirish Nidarmarthy_Kris Vaddi_Hagop Kantarjian_2020, place={Pavia, Italy}, title={Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders}, volume={105}, url={https://haematologica.org/article/view/9432}, DOI={10.3324/haematol.2019.229583}, abstractNote={Daily intravenous arsenic trioxide administered with all-trans retinoid acid, the standard-of-care for acute promyelocytic leukemia, is costly and challenging to administer. ORH-2014 is a novel, oral arsenic trioxide formulation, consisting of micron-size drug particles with rapid dissolution and high bioavailability. We conducted a multicenter phase 1 dose-escalating study in patients with advanced hematologic malignancies. Twelve patients received ORH-2014 at 5 mg (n=3), 10 mg (n=6), or 15 mg (n=3) orally once a day (fasted state). Objectives were to assess the safety, tolerability and pharmacokinetics of ORH-2014 to support a dose recommendation for future trials. The median age of the patients was 77 years (range: 45-81) and they had received a median of two (range: 1-5) prior therapies. There were no dose limiting toxicities and no drug-related severe adverse events, except one grade III QT prolongation occurring beyond the dose limiting toxicity assessment period and resolving after treatment interruption. ORH-2014 steady-state plasma concentration was reached on day 15. ORH-2014, 15 mg C<sub>max</sub> was comparable to the calculated approved dose of intravenous arsenic trioxide (mean [% coefficient of variation]: 114 [21%] <em>vs</em>. 124 [60%] ng/mL) and area under the curve from 0 to 24 hours was 2,140 (36%) <em>versus</em> 1,302 (30%) h*ng/mL. These results indicate that ORH-2014 at 15 mg is safe, bioavailable, and provides the required arsenic exposure compared to intravenous arsenic trioxide at the approved dose (0.15 mg/kg); this ORH-2014 dose is recommended for future trials. (<em>NCT03048344</em>; <a href="http://www.clin-icaltrials.gov">www.clin-icaltrials.gov</a&gt;).}, number={6}, journal={Haematologica}, author={Farhad Ravandi and Iphigenia Koumenis and Anandhi Johri and Martin Tallman and Gail J. Roboz and Stephen Strickland and Guillermo Garcia-Manero and Gautam Borthakur and Kiran Naqvi and Meghan Meyer and Madhu Pudipeddi and Sirish Nidarmarthy and Kris Vaddi and Hagop Kantarjian}, year={2020}, month={Jun.}, pages={1567-1574} }