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

Br J Haematol. 2010 Jul;150(1):58-71. doi: 10.1111/j.1365-2141.2010.08193.x. Epub 2010 Apr 16.

Abstract

The 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.

Trial registration: ClinicalTrials.gov NCT00093314.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / blood*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20 / immunology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infusions, Intravenous
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Male
  • Middle Aged
  • Models, Biological
  • Recurrence
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • Antineoplastic Agents
  • ofatumumab

Associated data

  • ClinicalTrials.gov/NCT00093314