title: Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study.
abstract: Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusions of ofatumumab at the following doses: (A) one 100 mg and three 500 mg; (B) one 300 mg and three 1000 mg; (C) one 500 mg and three 2000 mg. Sixty-seven percent of the patients were Binet stage B, and the median number of previous treatments was 3. The maximum tolerated dose was not reached. The majority of related adverse events occurred at first infusion, and the number of adverse events decreased at each subsequent infusion. Seventeen (51%) of 33 patients experienced infections, 88% of them of grade 1-2. One event of interstitial pneumonia was fatal; all other cases resolved within one month. The response rate of cohort C was 50% (13/26), one patient having a nodular partial remission and 12 patients partial remission. In conclusion, ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia (CLL) in doses up to 2000 mg. Preliminary data on safety and objective response are encouraging and support further studies on the role of ofatumumab in CLL patients. This trial was registered at www.clinicaltrials.gov as no. NCT00093314.
authors.affiliation: Département d'Hématologie, Centre Hospitalier Lyon Sud, Pierre-Benite Cedex, France. bertrand.coiffier@chu-lyon.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lepretre
authors.forename: Lars Møller
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Ole
authors.initials: O
authors.lastname: Gadeberg
authors.forename: Henrik
authors.initials: H
authors.lastname: Fredriksen
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: James
authors.initials: J
authors.lastname: Wooldridge
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.forename: Mimi
authors.initials: M
authors.lastname: Flensburg
authors.forename: Jørgen
authors.initials: J
authors.lastname: Petersen
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology*; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; C527517:ofatumumab