Phase I Study of Ofatumumab, a Human Anti-CD20 Antibody, in Japanese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Objectives: Ofatumumab is a human IgG1k monoclonal antibody that targets a membraneproximal epitope encompassing the small and large loops of CD20. This Phase I study evalu-ated the safety, tolerability, efficacy and pharmacokinetics of ofatumumab monotherapy inJapanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and smalllymphocytic 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 foursmall 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 infusionand either 500 or 1000 mg at seven subsequent weekly infusions.Results: No dose-limiting toxicities or serious adverse events were observed. Grade 3–4adverse events observed were grade 3 lymphocytopenia (n ¼ 1) and neutropenia (n ¼ 1).Grade 1–2 infusion-related adverse events leading to temporary interruption of ofatumumabinfusion were observed in all six patients on the first infusion day, and all patients completedthe planned eight infusions. The overall response rate was 50% (3/6).Conclusions: Ofatumumab was well tolerated at doses up to 1000 mg and showed prelimin-ary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/smalllymphocytic lymphoma, warranting further investigations. This study was registered atClinicalTrials.gov (NCT00742144).Key words: ofatumumab – chronic lymphocytic leukemia – small lymphocytic lymphoma – CD20 –monoclonal antibody