Tolerability and activity of ublituximab, umbralisib, and ibrutinib in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: a phase 1 dose escalation and expansion trial

Publication date: February 2019Source: The Lancet Haematology, Volume 6, Issue 2Author(s): Loretta J Nastoupil, Matthew A Lunning, Julie M Vose, Marshall T Schreeder, Tanya Siddiqi, Christopher R Flowers, Jonathon B Cohen, Jan A Burger, William G Wierda, Susan O'Brien, Peter Sportelli, Hari P Miskin, Michelle A Purdom, Michael S Weiss, Nathan H FowlerSummaryBackgroundTherapeutic approaches for B-cell malignancies continue to evolve, especially with regard to combination approaches. We assessed the safety and efficacy of the triplet ublituximab, umbralisib, and ibrutinib in patients with advanced B-cell malignancies.MethodsWe did an open-label, phase 1 study with dose-escalation and dose-expansion phases, at five centres in the USA. Eligible patients were aged 18 years or older with histologically confirmed lymphocytic leukaemia or relapsed or refractory B-cell non-Hodgkin lymphoma, had measurable disease, adequate organ function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Patients with known CNS lymphoma, active hepatitis B or C infection, or HIV were excluded. In the dose-escalation cohort, patients were treated in cycles of 28 days with escalating doses of oral umbralisib (400, 600, or 800 mg) and fixed doses of intravenous ublituximab (900 mg) and oral ibrutinib (420 mg for patients with chronic lymphocytic leukaemia; 560 mg for patients with B-cell non-Hodgkin lymphoma) in a standard 3 × 3 design until disease progression or int...
Source: The Lancet Haematology - Category: Hematology Source Type: research