# CLL12

Source: https://onco.cc/trials/cll12/  
OnCo record `cll12` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Ibrutinib 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.

## Fields

- Kind: Trial
- Status: mixed
- Last checked: 2026-09-22
- Also known as: GCLLSG CLL12
- Tags: soc-trials
- Registry id: 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
- Enrolled: 515
- 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.
- Outcomes: Overall survival at 5 years: Ibrutinib 420 mg daily 93.3% vs Placebo 93.6% vs Watch and wait (low-risk cohort, not randomised) 97.9%; Estimated overall survival at 10 years from diagnosis: Ibrutinib 420 mg daily 89.8% vs Placebo 86.5% vs Watch and wait (low-risk cohort, not randomised) 95.3%; Serious adverse events: Ibrutinib 420 mg daily 60% vs Placebo 60%

## Sources

- ClinicalTrials.gov NCT02863718: https://clinicaltrials.gov/study/NCT02863718

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/)
- technologies: [Active surveillance](https://onco.cc/technologies/active-surveillance/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Ibrutinib](https://onco.cc/drugs/ibrutinib/)
- companies: [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/)
- key papers: [CLL12: ibrutinib in early-stage chronic lymphocytic leukaemia, a randomised placebo-controlled phase 3 trial](https://onco.cc/key-papers/paper-cll12-ibrutinib-early-stage-langerbeins-jco-2025/)

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