Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders.

Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders. Haematologica. 2019 Sep 26;: Authors: Ravandi F, Koumenis I, Johri A, Tallman M, Roboz GJ, Strickland S, Garcia-Manero G, Borthakur G, Naqvi K, Meyer M, Pudipeddi M, Nidarmarthy S, Vaddi K, Kantarjian H Abstract 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. Median age of the patients was 77 years (range: 45-81) and they had received a median of 2 (range: 1-5) prior therapies. There were no dose limiting toxicities and no drug-related severe adverse events, except one Grade 3 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 Cmax was comparable to the c...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research