ELEVATE-TN
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia
Phase 3N = 535NCT02475681
- Population
- Treatment-naive CLL, age 65 years or older, or older than 18 and younger than 65 with creatinine clearance 30-69 mL/min or a Cumulative Illness Rating Scale for Geriatrics score above 6; ECOG performance status 2 or less
- Design
- Global open-label phase 3 study at 142 hospitals in 18 countries; patients randomly assigned 1:1:1. The primary endpoint was PFS, assessed by an independent review committee, between the two combination-therapy groups (acalabrutinib-obinutuzumab and obinutuzumab-chlorambucil). Crossover to acalabrutinib was allowed after progression on obinutuzumab-chlorambucil.
- Primary endpoint
- PFS
- Arms
- Acalabrutinib-obinutuzumab (experimental, n = 179): Acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, with obinutuzumab for cycles 2-7
- Acalabrutinib (experimental, n = 179): Acalabrutinib 100 mg twice daily until progression or unacceptable toxicity
- Obinutuzumab-chlorambucil (control, n = 177): Obinutuzumab for six cycles plus oral chlorambucil 0.5 mg/kg on days 1 and 15 of each cycle for six cycles
- People
- Sharman JP, senior author Byrd JC
PFSHR 0.10 (95% CI 0.06–0.17)Δ 24-month PFS+46 pointsPFSHR 0.20 (95% CI 0.13–0.30)Δ 24-month PFS+40 points
Show the numbers
| Endpoint | Analysis | Acalabrutinib-obinutuzumab / Acalabrutinib | Obinutuzumab-chlorambucil | Effect |
|---|---|---|---|---|
| PFSRandomly assigned patients (n=535); the abstract does not state the analysis population | primarymedian follow-up 28.3 monthsSharman 2020 | 93% at 2 y (87–96%) | median 22.6 months; 47% at 2 y (39–55%) | HR 0.10 (95% CI 0.06–0.17)P<0.0001Median PFS not reached with acalabrutinib-obinutuzumab. Estimated PFS at 24 months. This is the trial's primary comparison (independent review committee). |
| PFSRandomly assigned patients (n=535); the abstract does not state the analysis population | primarymedian follow-up 28.3 monthsSharman 2020 | 87% at 2 y (81–92%) | median 22.6 months; 47% at 2 y (39–55%) | HR 0.20 (95% CI 0.13–0.30)P<0.0001Median PFS not reached with acalabrutinib monotherapy. Estimated PFS at 24 months. The hazard ratio and its interval are printed as 0.20 and 0.13-0.3 in the abstract. |
| Endpoint | Analysis | Acalabrutinib-obinutuzumab / Acalabrutinib | Obinutuzumab-chlorambucil | Effect |
|---|---|---|---|---|
| PFSRandomly assigned patients (n=535); the abstract does not state the analysis population | primarymedian follow-up 28.3 monthsSharman 2020 | 93% at 2 y (87–96%) | median 22.6 months; 47% at 2 y (39–55%) | HR 0.10 (95% CI 0.06–0.17)P<0.0001Median PFS not reached with acalabrutinib-obinutuzumab. Estimated PFS at 24 months. This is the trial's primary comparison (independent review committee). |
| PFSRandomly assigned patients (n=535); the abstract does not state the analysis population | primarymedian follow-up 28.3 monthsSharman 2020 | 87% at 2 y (81–92%) | median 22.6 months; 47% at 2 y (39–55%) | HR 0.20 (95% CI 0.13–0.30)P<0.0001Median PFS not reached with acalabrutinib monotherapy. Estimated PFS at 24 months. The hazard ratio and its interval are printed as 0.20 and 0.13-0.3 in the abstract. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.1 | 0.06–0.17 |
| PFS | 0.2 | 0.13–0.3 |
- Obinutuzumab-chlorambucil (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Obinutuzumab-chlorambucil |
|---|---|
| 0 | 100.0% |
| 14 | 65.1% |
| 28 | 42.4% |
| 42 | 27.6% |
| 57 | 17.4% |
- Obinutuzumab-chlorambucil (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Obinutuzumab-chlorambucil |
|---|---|
| 0 | 100.0% |
| 14 | 65.1% |
| 28 | 42.4% |
| 42 | 27.6% |
| 57 | 17.4% |