CLL12
Ibrutinib versus placebo in treatment-naive, early-stage chronic lymphocytic leukemia (CLL12)
Phase 3N = 363NCT02863718
- Population
- Asymptomatic, treatment-naive Binet stage A CLL at increased risk of progression to symptomatic disease
- Design
- German CLL Study Group randomised, double-blind, placebo-controlled phase 3 trial; 363 asymptomatic, treatment-naive Binet stage A CLL patients at increased risk of progression randomly assigned 1:1 to ibrutinib 420 mg daily (n=182) or placebo (n=181). In addition, 152 low-risk patients were allocated to a non-randomised watch-and-wait cohort (final report); this cohort is not an arm of the randomised comparison and is not modelled as one. The ClinicalTrials.gov record lists 515 enrolled.
- Primary endpoint
- EFS
- Arms
- Ibrutinib (experimental, n = 182): Ibrutinib 420 mg daily
- Placebo (control, n = 181): Placebo daily
- People
- Langerbeins P, German CLL Study Group
EFSHR 0.25 (95% CI 0.14–0.43)Δ 60-month OS−0.3 points
Show the numbers
| Endpoint | Analysis | Ibrutinib | Placebo | Effect |
|---|---|---|---|---|
| EFSRandomly assigned patients (n=363) | primarymedian follow-up 31 monthsLangerbeins 2022 | — | median 47.8 months | HR 0.25 (95% CI 0.14–0.43)P<.0001Median EFS not reached in the ibrutinib group. Bleeding risk with ibrutinib 33.5% (abstract). |
| OSRandomly assigned patients (n=363); the abstract does not state the analysis population | finalmedian follow-up 69.3 monthsLangerbeins 2025 | 93.3% at 5 y (89.3–97.3%) | 93.6% at 5 y (89.5–97.7%) | Five-year survival rates. The abstract gives P=0.562 for the survival comparison (26 deaths) without naming the groups compared, so no P value is attached to an arm pair. Median observation time 69.3 months. Estimated 10-year survival from diagnosis: 89.8% (ibrutinib, 95% CI 83.3 to 96.3), 86.5% (placebo, 78.7 to 94.3). The separate non-randomised low-risk watch-and-wait cohort (n=152) had 5-year survival 97.9% (95% CI 95.6 to 100) and estimated 10-year survival from diagnosis 95.3% (91.1 to 99.4); it is not a control for the ibrutinib comparison. |
| Endpoint | Analysis | Ibrutinib | Placebo | Effect |
|---|---|---|---|---|
| EFSRandomly assigned patients (n=363) | primarymedian follow-up 31 monthsLangerbeins 2022 | — | median 47.8 months | HR 0.25 (95% CI 0.14–0.43)P<.0001Median EFS not reached in the ibrutinib group. Bleeding risk with ibrutinib 33.5% (abstract). |
| OSRandomly assigned patients (n=363); the abstract does not state the analysis population | finalmedian follow-up 69.3 monthsLangerbeins 2025 | 93.3% at 5 y (89.3–97.3%) | 93.6% at 5 y (89.5–97.7%) | Five-year survival rates. The abstract gives P=0.562 for the survival comparison (26 deaths) without naming the groups compared, so no P value is attached to an arm pair. Median observation time 69.3 months. Estimated 10-year survival from diagnosis: 89.8% (ibrutinib, 95% CI 83.3 to 96.3), 86.5% (placebo, 78.7 to 94.3). The separate non-randomised low-risk watch-and-wait cohort (n=152) had 5-year survival 97.9% (95% CI 95.6 to 100) and estimated 10-year survival from diagnosis 95.3% (91.1 to 99.4); it is not a control for the ibrutinib comparison. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.25 | 0.14–0.43 |
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Placebo |
|---|---|
| 0 | 100.0% |
| 30 | 64.7% |
| 60 | 41.9% |
| 90 | 27.1% |
| 120 | 17.5% |
Appears in
Sources
Langerbeins P, Zhang C, Robrecht S, Cramer P, Fürstenau M, Al-Sawaf O, et al. The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia. Blood. 2022;139(2):177-187.
Langerbeins P, Robrecht S, Nieper P, Cramer P, Fürstenau M, Al-Sawaf O, et al. Ibrutinib in Early-Stage Chronic Lymphocytic Leukemia: The Randomized, Placebo-Controlled, Double-Blind, Phase III CLL12 Trial. J Clin Oncol. 2025;43(4):392-402.