The CLL12 trial protocol: a placebo-controlled double-blind Phase III study of ibrutinib in the treatment of early-stage chronic lymphocytic leukemia patients with risk of early disease progression

Future Oncol. 2015;11(13):1895-903. doi: 10.2217/fon.15.95.

Abstract

Observation (watch and wait) is the standard of care for patients with asymptomatic Binet stage A chronic lymphocytic leukemia (CLL). However, the clinical course of these patients is very heterogeneous with some patients requiring treatment rather soon and others not progressing for ages. The clinical staging does not reflect this high variability of the clinical course of CLL. Published data demonstrate that the comprehensive use of several risk factors dramatically improves the accuracy of prognostication independent of clinical stage. The treatment of CLL underwent considerable changes with the introduction of kinase-inhibitors, including ibrutinib, an orally administered, well-tolerated and potent inhibitor of Bruton's tyrosine kinase. This is the first prospective, multicenter, placebo-controlled, double-blind, Phase III study to compare efficacy and safety of ibrutinib to a watch-and-wait approach in Binet stage A CLL with risk of disease progression defined by the comprehensive CLL score.

Keywords: B-cell receptor signaling; Binet A; Bruton's tyrosine kinase; CLL; ibrutinib; wait; watch.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenine / analogs & derivatives
  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Disease-Free Survival
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / pathology*
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Piperidines
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Risk

Substances

  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine