Phase I study of the oral mammalian target of rapamycin inhibitor everolimus (RAD001) in Japanese patients with relapsed or refractory non-Hodgkin lymphoma.

Phase I study was conducted to evaluate the safety, pharmacokinetics (PK) and efficacy of the oral mammalian target of rapamycin inhibitor, everolimus (RAD001), in patients with relapsed or refractory non-Hodgkin lymphoma (NHL). Patients received everolimus 5 or 10 mg orally once daily. Dose escalation was based on the safety assessment and the probability of dose-limiting toxicities (DLTs) using a Bayesian logistic model. DLTs were evaluated in six patients at each dose level during the initial 28 days of study treatment. A total of 13 patients were enrolled; 5 mg (seven) and 10 mg (six). No DLTs were observed at either dose level. Frequently observed potentially drug-related adverse events included leukopenia (8/13), thrombocytopenia (8/13), elevated hepatic transaminase (9/13), stomatitis (7/13), anemia (6/13), and nasopharyngitis (6/13). All adverse events were reversible. Non-infectious pneumonitis (grade 1) in one patient resolved following discontinuation of everolimus. Two patients with diffuse large B cell lymphoma and two patients with follicular lymphomas achieved objective responses with an overall response rate of 31% (4/13). The pharmacokinetic profiles were not different from those in non-Japanese patients. Everolimus was well tolerated at doses up to 10 mg/day and showed potential efficacy in relapsed or refractory NHL, warranting further investigation.