Phase I study of ofatumumab, a human anti-CD20 antibody, in Japanese patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma

Abstract

Objectives: Ofatumumab is a human IgG1κ monoclonal antibody that targets a membrane proximal epitope encompassing the small and large loops of CD20. This Phase I study evaluated the safety, tolerability, efficacy and pharmacokinetics of ofatumumab monotherapy in Japanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma.

Methods: Ofatumumab was administered intravenously weekly for a total of eight doses (dose escalation: 500 and 1000 mg). Six patients (two chronic lymphocytic leukemia and four small lymphocytic lymphoma) were enrolled into two dose cohorts (500 mg, three patients; 1000 mg, three patients). All six patients received 300 mg ofatumumab at the first infusion and either 500 or 1000 mg at seven subsequent weekly infusions.

Results: No dose-limiting toxicities or serious adverse events were observed. Grade 3-4 adverse events observed were grade 3 lymphocytopenia (n = 1) and neutropenia (n = 1). Grade 1-2 infusion-related adverse events leading to temporary interruption of ofatumumab infusion were observed in all six patients on the first infusion day, and all patients completed the planned eight infusions. The overall response rate was 50% (3/6).

Conclusions: Ofatumumab was well tolerated at doses up to 1000 mg and showed preliminary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, warranting further investigations.

Trial registration: ClinicalTrials.gov NCT00742144.

Figures

Figure 1.

Frequency of temporary infusion interruption due to AEs on each infusion day, Group 1, ofatumumab 500-mg infusion (n = 3); Group 2, ofatumumab 1000-mg infusion (n = 3). The first infusions were 300 mg for both infusion groups.

Figure 2.

(A) Individual CD19+CD5+ B-cell counts in the three patients in the 500-mg group; patients received 300 mg ofatumumab at the first infusion and seven subsequent once-weekly infusions of 500 mg. The time of administration of each of the eight ofatumumab doses is indicated by an arrow. (B) Individual CD19+CD5+ B-cell counts in the three patients in the 1000-mg group; patients received 300 mg ofatumumab at the first infusion and seven subsequent once-weekly infusions of 1000 mg. The time of administration of each of the eight ofatumumab doses is indicated by an arrow.

Figure 3.

(A) Individual plasma concentration of ofatumumab in the three patients in the 500-mg group; patients received 300 mg ofatumumab at the first infusion and seven subsequent once-weekly infusions of 500 mg. The time of administration of each of the eight ofatumumab doses is indicated by an arrow. (B) Individual plasma concentrations of ofatumumab in the three patients in the 1000-mg group; patients received 300-mg ofatumumab at the first infusion and seven subsequent once-weekly infusions of 1000 mg. The time of administration of each of the eight ofatumumab doses is indicated by an arrow.