Completed and ongoing trials including nonchemotherapy agents in patients with previously untreated MCL
| Agents (Trial) . | Study design . | Administration . | N . | Primary end point . | Secondary end points of interest . |
|---|---|---|---|---|---|
| Lenalidomide, bendamustine, rituximab, (Lena-Berit)15 | Phase 1-2 | Lenalidomide days 1-14, bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1 every 28 d ×6 cycles followed by single-agent lenalidomide days 1-21 cycles 7-13 | 51 | MTD lenalidomide omitted in cycle 1 then 10 mg in cycles 2-6; median PFS, 42 mo (95% CI, 31-53 mo) | CR/CRu, 64%; MRD-negative in blood, 42% |
| Ibrutinib, bendamustine, rituximab16 | Phase 1/1b | Ibrutinib 280 mg or 560 mg daily, bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1, ×6 cycles | 17 (including 5 previously untreated) | MTD ibrutinib 560 mg daily | ORR, 94%; CR, 76% |
| Lenalidomide, rituximab24 | Phase 2 | Induction: Lenalidomide 20 mg days 1-21 ×12 cycles, rituximab 375 mg/m2 weekly ×4 then day 1 of cycles 4, 6, 8, 10, 12 | 38 | ORR, 87% | 2-y PFS, 85% (95% CI, 67%-94%) |
| Maintenance: Lenalidomide 15 mg days 1-21 of each cycle, rituximab 375 mg/m2 q8 wk until progression | |||||
| Ibrutinib, rituximab23 | Phase 2 | Ibrutinib 560 mg daily, rituximab 375 mg/m2 weekly ×4 then day 1 of cycles 3-12 | 50 | ORR, 100% (36 of 36 evaluable) | CR, 100% (19 of 19 evaluable) |
| Ibrutinib, bendamustine, rituximab (SHINE) NCT01776840 | Randomized phase 3 | Induction: Ibrutinib 560 mg vs placebo daily, plus bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1 q28 ×6 cycles | ∼524 | PFS (estimated 28 March 2018) | OS |
| Maintenance: ibrutinib 560 mg vs placebo daily until progression, plus rituximab 375 mg/m2 q8 wk ×2 y | |||||
| Bortezomib, bendamustine, rituximab (E1411) NCT01415752 | Randomized phase 2 | Induction: Bortezomib 1.8 mg/m2 days 1, 8, 15 vs nothing, plus bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1 q28 d ×6 cycles | ∼332 | 2-y PFS for RB vs RBV | CR |
| Maintenance: Lenalidomide 20 mg days 1-21 q28 d vs nothing, plus rituximab 375 mg/m2 q8 wk ×2 y | PFS for R2 vs R | ||||
| Ibrutinib, rituximab (ENRICH) CRUK/14/026 | Randomized phase 3 | Ibrutinib 560 mg daily until progression, rituximab 375 mg/m2 q3-4 wk ×6 then q8 wk × 2 y vs R-CHOP or RB followed by rituximab q8 wk ×2 y | |||
| Ibrutinib, R-CHOP/R-DHAP (Triangle) NCT02858258 | Randomized phase 3 | R-CHOP/R-DHAP/ASCT vs R-CHOP/R-DHAP + I/ASCT + I vs R-CHOP/R-DHAP + I | ∼870 | FFS (estimated May 2021) | OS |
| Agents (Trial) . | Study design . | Administration . | N . | Primary end point . | Secondary end points of interest . |
|---|---|---|---|---|---|
| Lenalidomide, bendamustine, rituximab, (Lena-Berit)15 | Phase 1-2 | Lenalidomide days 1-14, bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1 every 28 d ×6 cycles followed by single-agent lenalidomide days 1-21 cycles 7-13 | 51 | MTD lenalidomide omitted in cycle 1 then 10 mg in cycles 2-6; median PFS, 42 mo (95% CI, 31-53 mo) | CR/CRu, 64%; MRD-negative in blood, 42% |
| Ibrutinib, bendamustine, rituximab16 | Phase 1/1b | Ibrutinib 280 mg or 560 mg daily, bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1, ×6 cycles | 17 (including 5 previously untreated) | MTD ibrutinib 560 mg daily | ORR, 94%; CR, 76% |
| Lenalidomide, rituximab24 | Phase 2 | Induction: Lenalidomide 20 mg days 1-21 ×12 cycles, rituximab 375 mg/m2 weekly ×4 then day 1 of cycles 4, 6, 8, 10, 12 | 38 | ORR, 87% | 2-y PFS, 85% (95% CI, 67%-94%) |
| Maintenance: Lenalidomide 15 mg days 1-21 of each cycle, rituximab 375 mg/m2 q8 wk until progression | |||||
| Ibrutinib, rituximab23 | Phase 2 | Ibrutinib 560 mg daily, rituximab 375 mg/m2 weekly ×4 then day 1 of cycles 3-12 | 50 | ORR, 100% (36 of 36 evaluable) | CR, 100% (19 of 19 evaluable) |
| Ibrutinib, bendamustine, rituximab (SHINE) NCT01776840 | Randomized phase 3 | Induction: Ibrutinib 560 mg vs placebo daily, plus bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1 q28 ×6 cycles | ∼524 | PFS (estimated 28 March 2018) | OS |
| Maintenance: ibrutinib 560 mg vs placebo daily until progression, plus rituximab 375 mg/m2 q8 wk ×2 y | |||||
| Bortezomib, bendamustine, rituximab (E1411) NCT01415752 | Randomized phase 2 | Induction: Bortezomib 1.8 mg/m2 days 1, 8, 15 vs nothing, plus bendamustine 90 mg/m2 days 1 + 2, rituximab 375 mg/m2 day 1 q28 d ×6 cycles | ∼332 | 2-y PFS for RB vs RBV | CR |
| Maintenance: Lenalidomide 20 mg days 1-21 q28 d vs nothing, plus rituximab 375 mg/m2 q8 wk ×2 y | PFS for R2 vs R | ||||
| Ibrutinib, rituximab (ENRICH) CRUK/14/026 | Randomized phase 3 | Ibrutinib 560 mg daily until progression, rituximab 375 mg/m2 q3-4 wk ×6 then q8 wk × 2 y vs R-CHOP or RB followed by rituximab q8 wk ×2 y | |||
| Ibrutinib, R-CHOP/R-DHAP (Triangle) NCT02858258 | Randomized phase 3 | R-CHOP/R-DHAP/ASCT vs R-CHOP/R-DHAP + I/ASCT + I vs R-CHOP/R-DHAP + I | ∼870 | FFS (estimated May 2021) | OS |
ASCT, autologous stem cell transplantation; CI, confidence interval; CR, complete response; CRu, complete response unconfirmed; FFS, failure-free survival; I, ibrutinib; MRD, minimal residual disease; MTD, maximum tolerated dose; ORR, overall response rate; PFS, progression-free survival; q3-4, every 3-4 weeks; q8, every 8 weeks; q28, every 28 days; R, rituximab; R2, lenalidomide, rituximab; RB, rituximab, bendamustine; RBV, rituximab, bendamustine, bortezomib; R-CHOP, rituximab, cyclophosphamide, adriamycin, vincristine, prednisone; R-DHAP, rituximab, dexamethasone, cytarabine, cisplatin.