Summary of time-limited frontline trials
| Reference . | Trial . | Patients . | Primary end point . | Results . |
|---|---|---|---|---|
| Randomized phase 3 trials | ||||
| Shanafelt et al17 , ECOG1912 | FCR vs I-R | Age <70 no del 17p N = 529 | PFS FU: 33.6 mo | I - R > FCR (89.4% vs 72.9% at 3 y; HR: 0.35; 95% CI, 0.22-0.56; P < .001) OS: I - R > FCR (98.8% vs 91.5% at 3 y) HR: 0.17; 95% CI, 0.05-0.54; P < .001 |
| Al-Sawaf et al3 , CLL14 | CLB-O vs VEN-O | CIRS >6 and/or Cl. creat 30-69 mL/min N = 432 | PFS FU: 39.6 mo | VEN-O > CLB-O (NE vs 35.5 mo) HR: 0.31, 95% CI, 0.22–0.44; P < .0001 |
| Woyach et al1 , ALLIANCE | BR/I-R/I | Age >65 N = 447 | PFS FU: 38 mo | I-R > BR. HR: 0.38; 95% CI, 0.25-0.59; P < .001 I > BR. HR: 0.39; 95% CI, 0.26-0.58; P < .001 |
| Kater et al23 , GLOW | VEN-I/CLB-O | Age >65 or CIRS >6 or Cl. creat <70 mL/min N = 211 | PFS FU: 27.7 mo | VEN-I > CLB-O HR: 0.216 (95% CI, 0.131-0.357); p < .0001) |
| Phase 2 trials | ||||
| Michallet et al24 , ICLL07 | I-O+/−4 courses FCO-I | Fit patients, no del 17p or p53 N = 135 | CR + BM MRD <0.01% FU: 26.3 | CR + MRD <0.01%: 62% (95% CI 55% to 69%) |
| Davids et al25 | FCR 6 courses-I (stop 2 y if BM uMRD) | Age <65 N = 85 | CR + BM uMRD 2 mo post FCR FU: 16.5 mo | CR + BM uMRD: 33%, (95% CI 23-44%) |
| Jain et al27 | VEN-I | Del17P and/or TP53 mut and/or del11q and/or U-IGHV and/or age >65 N = 80 | CR + CRi FU: 14.8 mo | CR + CRi: 88%, CR + uMRD: 61% |
| Wierda et al28 , CAPTIVATE | VEN-I uMRD : I vs placebo MRD+ : I vs V-I | Age <70 N = 164 | 1 y DFS FU: NA | I vs placebo: NS (95% vs 100%) 30-mo PFS ∼95% in all arms |
| Reference . | Trial . | Patients . | Primary end point . | Results . |
|---|---|---|---|---|
| Randomized phase 3 trials | ||||
| Shanafelt et al17 , ECOG1912 | FCR vs I-R | Age <70 no del 17p N = 529 | PFS FU: 33.6 mo | I - R > FCR (89.4% vs 72.9% at 3 y; HR: 0.35; 95% CI, 0.22-0.56; P < .001) OS: I - R > FCR (98.8% vs 91.5% at 3 y) HR: 0.17; 95% CI, 0.05-0.54; P < .001 |
| Al-Sawaf et al3 , CLL14 | CLB-O vs VEN-O | CIRS >6 and/or Cl. creat 30-69 mL/min N = 432 | PFS FU: 39.6 mo | VEN-O > CLB-O (NE vs 35.5 mo) HR: 0.31, 95% CI, 0.22–0.44; P < .0001 |
| Woyach et al1 , ALLIANCE | BR/I-R/I | Age >65 N = 447 | PFS FU: 38 mo | I-R > BR. HR: 0.38; 95% CI, 0.25-0.59; P < .001 I > BR. HR: 0.39; 95% CI, 0.26-0.58; P < .001 |
| Kater et al23 , GLOW | VEN-I/CLB-O | Age >65 or CIRS >6 or Cl. creat <70 mL/min N = 211 | PFS FU: 27.7 mo | VEN-I > CLB-O HR: 0.216 (95% CI, 0.131-0.357); p < .0001) |
| Phase 2 trials | ||||
| Michallet et al24 , ICLL07 | I-O+/−4 courses FCO-I | Fit patients, no del 17p or p53 N = 135 | CR + BM MRD <0.01% FU: 26.3 | CR + MRD <0.01%: 62% (95% CI 55% to 69%) |
| Davids et al25 | FCR 6 courses-I (stop 2 y if BM uMRD) | Age <65 N = 85 | CR + BM uMRD 2 mo post FCR FU: 16.5 mo | CR + BM uMRD: 33%, (95% CI 23-44%) |
| Jain et al27 | VEN-I | Del17P and/or TP53 mut and/or del11q and/or U-IGHV and/or age >65 N = 80 | CR + CRi FU: 14.8 mo | CR + CRi: 88%, CR + uMRD: 61% |
| Wierda et al28 , CAPTIVATE | VEN-I uMRD : I vs placebo MRD+ : I vs V-I | Age <70 N = 164 | 1 y DFS FU: NA | I vs placebo: NS (95% vs 100%) 30-mo PFS ∼95% in all arms |
A, acalabrutinib; B, bendamustine; C, Cyclophosphamide; Cl. creat, clearing of creatine; CR, complete remission; DFS, disease-free survival; F, Fludarabine; FU, median follow-up; I, ibrutinib; NA, not applicable; NE, not evaluable; NS, not significant; O, obinutuzumab; OS, overall survival; PFS, progression-free survival; R, rituximab; VEN, venetoclax.