{"entity":{"id":"cll12","kind":"trial","name":"CLL12","aka":["GCLLSG CLL12"],"tldr":"CLL12 asked whether starting the pill ibrutinib early, before chronic lymphocytic leukaemia causes symptoms, is better than the usual practice of watching and waiting; early treatment delayed the disease but after nearly six years of follow-up people lived just as long either way, so watch and wait remains the standard.","summary":"CLL12 was the German CLL Study Group's randomised, double-blind, placebo-controlled phase 3 trial that reassessed the watch-and-wait consensus in the era of targeted drugs. 363 patients with asymptomatic Binet stage A chronic lymphocytic leukaemia at increased risk of progression (by a validated score) were randomised to ibrutinib 420 mg daily or placebo; a further 152 low-risk patients were followed without treatment. The primary endpoint was event-free survival.\n\nIbrutinib significantly delayed progression to symptomatic disease, but at a median observation of 69.3 months overall survival was the same: five-year survival 93.3 percent with ibrutinib, 93.6 percent with placebo and 97.9 percent in the watch-and-wait cohort. Cardiovascular toxicity was more common with ibrutinib. The authors conclude that watch and wait remains the standard of care for early-stage disease whatever the risk profile, and that is how the corpus's chronic lymphocytic leukaemia page cites the trial.","status":"mixed","asOf":"2026-09-22","links":[{"label":"ClinicalTrials.gov NCT02863718","url":"https://clinicaltrials.gov/study/NCT02863718"}],"tags":["soc-trials"],"related":[],"cancers":["cll","cll-treatment-naive","leukaemia"],"sections":[],"technologies":["kinase-inhibitors","active-surveillance"],"targets":[],"drugs":["ibrutinib"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cll12-ibrutinib-early-stage-langerbeins-jco-2025"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02863718","phase":"3","setting":"Asymptomatic, untreated Binet stage A chronic lymphocytic leukaemia at increased risk of early progression: ibrutinib 420 mg daily or placebo (double-blind), with a low-risk cohort followed on watch and wait","sponsor":"German CLL Study Group","result":"Ibrutinib delayed progression to symptomatic disease but did not improve survival: five-year overall survival 93.3 percent against 93.6 percent with placebo; watch and wait remains standard for early-stage disease.","yearReported":2024,"enrolled":515,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Ibrutinib 420 mg daily","n":182,"value":93.3,"note":"95% CI 89.3 to 97.3; median observation 69.3 months"},{"name":"Placebo","n":181,"value":93.6,"note":"95% CI 89.5 to 97.7"},{"name":"Watch and wait (low-risk cohort, not randomised)","n":152,"value":97.9,"note":"95% CI 95.6 to 100"}],"source":"https://doi.org/10.1200/jco.24.00975"},{"endpoint":"Estimated overall survival at 10 years from diagnosis","unit":"%","arms":[{"name":"Ibrutinib 420 mg daily","value":89.8},{"name":"Placebo","value":86.5},{"name":"Watch and wait (low-risk cohort, not randomised)","value":95.3}],"source":"https://doi.org/10.1200/jco.24.00975"},{"endpoint":"Serious adverse events","unit":"%","arms":[{"name":"Ibrutinib 420 mg daily","value":60,"note":"Reported for both treatment groups together; more cardiovascular toxicity with ibrutinib"},{"name":"Placebo","value":60}],"source":"https://doi.org/10.1200/jco.24.00975"}]},"route":"/trials/cll12/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"}],"technology":[{"id":"active-surveillance","kind":"technology","name":"Active surveillance","route":"/technologies/active-surveillance/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"paper":[{"id":"paper-cll12-ibrutinib-early-stage-langerbeins-jco-2025","kind":"paper","name":"CLL12: ibrutinib in early-stage chronic lymphocytic leukaemia, a randomised placebo-controlled phase 3 trial","route":"/key-papers/paper-cll12-ibrutinib-early-stage-langerbeins-jco-2025/"}]}}