UNLABELLED: Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median Cmax and Ctrough values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher Cmax and Ctrough values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00410163).

b UCSD Moores Cancer Center La Jolla CA USA

c Klinik für Hämatologie Universitätsklinikum Essen Essen Germany

e Department of Internal Medicine 3 Universitätsklinikum Ulm Ulm Germany

f 4th Department of Internal Medicine Hematology University Hospital and Faculty of Medicine Hradec Králové Czech Republic

g Department of Internal Medicine Hemato Oncology University Hospital Brno Brno Czech Republic

Genmab Copenhagen Denmark

h Johannes Gutenberg University Mainz Germany

i Roswell Park Cancer Institute Buffalo NY USA

j Cancer Therapy and Research Center San Antonio TX USA

k Pharstat Inc Raleigh NC USA

l GlaxoSmithKline Collegeville PA USA

m Novartis Pharmaceuticals King of Prussia PA USA

Novartis Pharmaceuticals Morrisville NC USA

o MD Anderson Cancer Center The University of Texas Houston TX USA

Vilnius University Hospital Santariskiu Klinikos Vilnius University Vilnius Lithuania

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NCT00410163