Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1–2 study
Copyright policy )Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1–2 study
SummaryThe purpose of this phase 1–2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumumab concentration profiles were fitted well by a two‐compartment model with different elimination rate constant at first infusion compared to the remaining infusions in line with the observed rapid and sustained B‐cell depletion. Exposure to ofatumumab was linked to clinical outcomes: high exposure was associated with higher probability of overall clinical response and longer progression‐free survival. This association still remained statistically significant even when adjusting for relevant baseline covariates including tumour burden. The trial was registered at http://www.clinicaltrials.gov (NCT00093314).
- Amsterdam UMC Netherlands
- University of Amsterdam Netherlands
- Wrocław Medical University Poland
- Centre Hospitalier Lyon Sud France
- University of Iowa United States
Male, Dose-response relationship, Models, Recurrence, Monoclonal, 80 and over, Chronic, Treatment outcome, B-cell - blood, Middle aged, Infusions, Intravenous, intraosseous, Aged, 80 and over, Leukemia, CD20 - immunology, drug, Antibodies, Monoclonal, Middle Aged, Lymphocytic, Antineoplastic agents - therapeutic use, chronic, Treatment Outcome, monoclonal - therapeutic use, Female, Drug, Intravenous, Adult, Infusions, B-cell - drug therapy, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Models, Biological, Antibodies, Dose-Response Relationship, Humans, CD20, Antigens, intravenous infusion, Aged, Dose-Response Relationship, Drug, B-Cell, PK/PD, Survival analysis, Biological, monoclonal - blood, Antigens, CD20, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Antineoplastic agents - administration & dosage, chronic lumphocytic leukaemia, monoclonal - administration & dosage, lymphocytic, monoclonal antibody, biological, ofatumumab
Male, Dose-response relationship, Models, Recurrence, Monoclonal, 80 and over, Chronic, Treatment outcome, B-cell - blood, Middle aged, Infusions, Intravenous, intraosseous, Aged, 80 and over, Leukemia, CD20 - immunology, drug, Antibodies, Monoclonal, Middle Aged, Lymphocytic, Antineoplastic agents - therapeutic use, chronic, Treatment Outcome, monoclonal - therapeutic use, Female, Drug, Intravenous, Adult, Infusions, B-cell - drug therapy, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Models, Biological, Antibodies, Dose-Response Relationship, Humans, CD20, Antigens, intravenous infusion, Aged, Dose-Response Relationship, Drug, B-Cell, PK/PD, Survival analysis, Biological, monoclonal - blood, Antigens, CD20, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Antineoplastic agents - administration & dosage, chronic lumphocytic leukaemia, monoclonal - administration & dosage, lymphocytic, monoclonal antibody, biological, ofatumumab
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