Ofatumumab Combined With Fludarabine and Cyclophosphamide (O-FC) Shows High Activity in Patients With Previously Untreated Chronic Lymphocytic Leukemia: Results From a Randomized, Multicenter, International, Two-Dose, Parallel-Group Phase II Trial

Abstract

Introduction: Chemoimmunotherapy regimens have become the treatment standard for patients with CLL. Ofatumumab is a human monoclonal antibody that targets a unique small-loop epitope on CD20 and elicits rapid and efficient in vitro complement-dependent cytotoxicity, as well as antibody-dependent cellular cytotoxicity. Recent studies demonstrated single-agent ofatumumab activity, with high overall response rates (ORR) in patients with refractory CLL. We conducted an international, randomized, parallel group, Phase II trial with two doses of ofatumumab combined with fludarabine and cyclophosphamide (FC) in previously untreated patients with CLL to evaluate the efficacy and tolerability of this chemoimmunotherapy regimen. Methods: Previously untreated patients (N=61) with active CLL (by NCI-WG guidelines) were randomized to receive ofatumumab 500 mg (Group A) or 1000 mg (Group B) on day 1, combined with fludarabine (25 mg/m2 IV daily; days 1–3) and cyclophosphamide (250 mg/m2 IV daily; days 1–3) every 4 weeks for a total of 6 courses. In both Groups, the first dose of ofatumumab was 300 mg. Dose reduction of FC, but not ofatumumab, was allowed. Premedication for ofatumumab was paracetamol and antihistamine prior to each infusion, and glucocorticoid prior to infusions 1 and 2. Neutrophil growth factor and anti-infective prophylaxis were not mandated. The primary endpoint was complete response (CR) rate (1996 NCI-WG criteria) assessed by an Independent Review Committee (IRC), measured from the start of treatment until 3 months after the last infusion. Safety evaluations included investigator-reported adverse events (AEs) and deaths. Follow-up continues for collection of time-to-event endpoints. Results: Data from all 61 patients were available for response assessment (primary endpoint). Pretreatment characteristics are shown in the Table.[...].