CLL12
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.
Overview
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.
- 93.3 vs 93.6 out of 100 alive at 5 years with Ibrutinib 420 mg daily compared with Placebo; 0.3 fewer per 100.
- On this measure the first group did worse, not better.
- Other groups: Watch and wait (low-risk cohort, not randomised) 97.9 of 100.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 89.8 vs 86.5 out of 100 alive at 10 years with Ibrutinib 420 mg daily compared with Placebo; 3.3 more per 100.
- Roughly one extra person helped for every 30 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Other groups: Watch and wait (low-risk cohort, not randomised) 95.3 of 100.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 60 vs 60 out of 100 reached this endpoint with Ibrutinib 420 mg daily compared with Placebo; 0 more per 100.
- No difference between the groups on this measure.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: 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. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
515 enrolled.
95% CI 89.3 to 97.3; median observation 69.3 months · 95% CI 89.5 to 97.7 · 95% CI 95.6 to 100
SourceReported for both treatment groups together; more cardiovascular toxicity with ibrutinib
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival at 5 years | Ibrutinib 420 mg daily | 182 | 93.3% | - | - | link |
| Placebo | 181 | 93.6% | ||||
| Watch and wait (low-risk cohort, not randomised) | 152 | 97.9% | ||||
| Estimated overall survival at 10 years from diagnosis | Ibrutinib 420 mg daily | - | 89.8% | - | - | link |
| Placebo | - | 86.5% | ||||
| Watch and wait (low-risk cohort, not randomised) | - | 95.3% | ||||
| Serious adverse events | Ibrutinib 420 mg daily | - | 60% | - | - | link |
| Placebo | - | 60% |
Similar pages
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- TrialGRAALL-2005
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- TrialIntReALL SR 2010
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- TrialQUAZAR AML-001
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