A phase I study of obinutuzumab induction followed by two years of maintenance in patients with relapsed CD20-positive B-cell malignancies
Mené sur 22 patients atteints d'un lymphome non hodgkinien CD20+ récidivant ou d'une leucémie lymphocytaire chronique, cet essai de phase I évalue la toxicité et l'activité antitumorale de l'obinutuzumab, un anticorps anti-CD20
This phase I study evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by two years of maintenance. Cohorts of 3-6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months for a maximum of 8 doses. Twenty-two patients with relapsed CD20-positive non-Hodgkin lymphoma or chronic lymphocytic leukemia with an indication for treatment and no therapy of higher priority were enrolled. Patients received a median of 4 prior regimens; 86% had received at least one rituximab-containing regimen. No dose limiting or unexpected adverse events were observed. Infusion-related reactions were most common (all grades 73%, grade 3/4 18%), followed by infection (32%), pyrexia (23%), neutropenia (23%), headache (18%) and nausea (18%). At end of induction, 5 (23%) patients achieved a partial response and 12 (54%) had stable disease. Eight patients received maintenance; best overall response was 32% (6 PR/1 CR). Obinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pre-treated population and warrants further investigation. This study was registered at ClinicalTrials.gov (identifier NCT00576758).
Blood 2012