title: 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.
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.
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Langerbeins
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bahlo
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rhein
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Natali
authors.initials: N
authors.lastname: Pflug
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department III of Internal Medicine, University Hospital, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Karl Anton
authors.initials: KA
authors.lastname: Kreuzer
authors.affiliation: Department I of Internal Medicine, Clinical Center Schwabing, Munich, Germany.
authors.forename: Clemens-Martin
authors.initials: CM
authors.lastname: Wendtner
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Eichhorst
authors.affiliation: Department I of Internal Medicine, Center of Integrated Oncology (CIO), & CECAD - Cluster of Excellence 'Cellular Stress Responses in Aging-Associated Diseases,' University of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010880:Piperidines; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012306:Risk
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
keywords: B-cell receptor signaling; Binet A; Bruton's tyrosine kinase; CLL; ibrutinib; wait; watch