Trials including nonchemotherapy agents in patients with previous MCL
| Agents (Trial) . | Study design . | Administration . | N . | Primary end point . | Secondary end points . |
|---|---|---|---|---|---|
| Temsirolimus, bendamustine, rituximab (BerT)35 | Phase 1-2 | Temsirolimus in doses from 25 to 75 mg added on days 1, 8, 15, bendamustine 90 mg/m2 day 1 + 2, and rituximab 375 mg/m2 day 1 q28 d | 29 MCL | Phase 1: temsirolimus 50 mg days 1, 8, 15 | Median PFS, 33 mo |
| Phase 2: ORR 92% | |||||
| Ibrutinib, bendamustine, ibrutinib16 | 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, bendamustine, rituximab (R2B)36 | Phase 2 | Induction: Lenalidomide 10 mg on days 1-14, bendamustine 70 mg/m2 on days 2 and 3, rituximab 375 mg/m2 on day 8 of cycle 1 and thereafter on day 1 q28 d ×4 cycles | 42 | CR, 55% | Median PFS, 20 mo |
| Consolidation: rituximab 375 mg/m2 on day 1, plus lenalidomide 15 mg daily on days 1-21 every 28 d | |||||
| Maintenance: Lenalidomide 15 mg daily on days 1-21 every 28 d for up to 18 cycles | |||||
| Lenalidomide, rituximab58 | Phase 1-2 | Rituximab 375 mg/m2 weekly ×4 plus | 52 | Phase 1: MTD lenalidomide 20 mg | Median PFS, 11.1 mo |
| Phase 1: escalating doses of lenalidomide days 1-21 | Phase 2: ORR, 57% | Median DoR, 18.9 mo | |||
| Phase 2: lenalidomide 20 mg days 1-21 | |||||
| Ibrutinib, rituximab38 | Phase 2 | Ibrutinib 560 mg daily, rituximab 375 mg/m2 weekly ×4 then day 1 of cycles 3-12 | 50 | ORR, 88% | CR, 44% |
| Ibrutinib, lenalidomide, rituximab (PHELEMON)22 | Phase 2 | Lenalidomide 15 mg days 1-21, ibrutinib 560 mg daily, rituximab 375 mg/m2 days 1, 8, 15, 22 in cycle 1 then day 1 in cycles 3, 5, 7, 9, 11 for 12 cycles followed by ibrutinib 560 mg daily, rituximab 375 mg/m2 day 1 of each cycle until progression | 50 | ORR, 83% | CR, 41% |
| MRD−, 7 of 12 in blood | |||||
| Ibrutinib, palbociclib43 | Phase 1 | Ibrutinib (escalating dose) daily, palbociclib (escalating dose) days 1-21 until progression | 23 (preliminary) | MTD ibrutinib 560 mg daily, palbociclib 100 mg days 1-21 | ORR, 63%; CR, 41%; 1-y DoR, 100% |
| Ibrutinib, venetoclax42 | Phase 2 | Ibrutinib 560 mg daily, venetoclax escalating doses (target 400 mg daily) | 8 (preliminary) | ORR, 4 of 5 evaluable | |
| Ibrutinib, venetoclax41 | Phase 1/1b | Ibrutinib escalating doses, venetoclax escalating doses | 8 (preliminary) | MTD: not yet reached | |
| Ibrutinib, venetoclax, obinutuzumab NCT | Phase 1-2 | Ibrutinib, obinutuzumab, venetoclax | ∼33 | MTD | ORR; CR |
| Agents (Trial) . | Study design . | Administration . | N . | Primary end point . | Secondary end points . |
|---|---|---|---|---|---|
| Temsirolimus, bendamustine, rituximab (BerT)35 | Phase 1-2 | Temsirolimus in doses from 25 to 75 mg added on days 1, 8, 15, bendamustine 90 mg/m2 day 1 + 2, and rituximab 375 mg/m2 day 1 q28 d | 29 MCL | Phase 1: temsirolimus 50 mg days 1, 8, 15 | Median PFS, 33 mo |
| Phase 2: ORR 92% | |||||
| Ibrutinib, bendamustine, ibrutinib16 | 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, bendamustine, rituximab (R2B)36 | Phase 2 | Induction: Lenalidomide 10 mg on days 1-14, bendamustine 70 mg/m2 on days 2 and 3, rituximab 375 mg/m2 on day 8 of cycle 1 and thereafter on day 1 q28 d ×4 cycles | 42 | CR, 55% | Median PFS, 20 mo |
| Consolidation: rituximab 375 mg/m2 on day 1, plus lenalidomide 15 mg daily on days 1-21 every 28 d | |||||
| Maintenance: Lenalidomide 15 mg daily on days 1-21 every 28 d for up to 18 cycles | |||||
| Lenalidomide, rituximab58 | Phase 1-2 | Rituximab 375 mg/m2 weekly ×4 plus | 52 | Phase 1: MTD lenalidomide 20 mg | Median PFS, 11.1 mo |
| Phase 1: escalating doses of lenalidomide days 1-21 | Phase 2: ORR, 57% | Median DoR, 18.9 mo | |||
| Phase 2: lenalidomide 20 mg days 1-21 | |||||
| Ibrutinib, rituximab38 | Phase 2 | Ibrutinib 560 mg daily, rituximab 375 mg/m2 weekly ×4 then day 1 of cycles 3-12 | 50 | ORR, 88% | CR, 44% |
| Ibrutinib, lenalidomide, rituximab (PHELEMON)22 | Phase 2 | Lenalidomide 15 mg days 1-21, ibrutinib 560 mg daily, rituximab 375 mg/m2 days 1, 8, 15, 22 in cycle 1 then day 1 in cycles 3, 5, 7, 9, 11 for 12 cycles followed by ibrutinib 560 mg daily, rituximab 375 mg/m2 day 1 of each cycle until progression | 50 | ORR, 83% | CR, 41% |
| MRD−, 7 of 12 in blood | |||||
| Ibrutinib, palbociclib43 | Phase 1 | Ibrutinib (escalating dose) daily, palbociclib (escalating dose) days 1-21 until progression | 23 (preliminary) | MTD ibrutinib 560 mg daily, palbociclib 100 mg days 1-21 | ORR, 63%; CR, 41%; 1-y DoR, 100% |
| Ibrutinib, venetoclax42 | Phase 2 | Ibrutinib 560 mg daily, venetoclax escalating doses (target 400 mg daily) | 8 (preliminary) | ORR, 4 of 5 evaluable | |
| Ibrutinib, venetoclax41 | Phase 1/1b | Ibrutinib escalating doses, venetoclax escalating doses | 8 (preliminary) | MTD: not yet reached | |
| Ibrutinib, venetoclax, obinutuzumab NCT | Phase 1-2 | Ibrutinib, obinutuzumab, venetoclax | ∼33 | MTD | ORR; CR |
CR, complete response; DoR, duration of response; MRD, minimal residual disease; MTD, maximum tolerated dose; ORR, overall response rate; q28, every 28 days.