Table 2.
Selected ongoing clinical trials with proteasome inhibitors in multiple myeloma
| Proteasome inhibitor under evaluation | Trial phase, interventions, and primary end point | Schedule | Patient population | Reference |
|---|---|---|---|---|
| Bortezomib | Phase III VRD versus RD PFS |
VRD: bortezomib s.c. or i.v. on days 1, 4, 8 and 11; lenalidomide on days 1–14; dexamethasone p.o.on days 1, 2, 4, 5, 8, 9, 11 and 12 of 21-day cycles for 8 cycles (in the absence of disease progression or unacceptable toxicities) RD: lenalidomide p.o. on days 1–21; dexamethasone on days 1, 8, 15 and 22 of 28-day cycles for 6 cycles (in the absence of disease progression or unacceptable toxicities) |
NDMM without an intent for immediate aSCT | NCT01530594144 |
| Bortezomib and carfilzomib | Phase III VRD versus CRD 2 years of lenalidomide maintenance versus indefinite maintenance OS |
VRD: bortezomib s.c. or i.v. on days 1, 4, 8 and 11 of cycles 1–8 and on days 1 and 8 of cycles 9–12; lenalidomide p.o. on days 1–14 of all cycles; dexamethasone p.o. on days 1, 2, 4, 5, 8, 9, 11 and 12 of cycles 1–8 and on days 1, 2, 8 and 9 of cycles 9–12 of 21-day cycles CRD: carfilzomib i.v. on days 1, 2, 8, 9, 15 and 16; lenalidomide p.o.on days 1–21; dexamethasone p.o. on days 1, 8, 15 and 22 of 28-day cycles for 9 cycles 2 years of lenalidomide: lenalidomide p.o. on days 1–21 of 28-day cycles for 24 cycles (in the absences of disease progression or unacceptable toxicities) Indefinite maintenance: lenalidomide p.o. on days 1–21 of 28-day cycles (in the absence of disease progression or unacceptable toxicities) |
NDMM | NCT0186355049 |
| Bortezomib and carfilzomib | Phase III CMP versus VMP OS |
CMP: carfilzomib 20/36 mg/m2 i.v. on days 1, 2, 8, 9, 22, 23, 29 and 30; melphalan p.o.; prednisone 60 mg/m2 p.o. days 1–4 for 9 cycles VMP: bortezomib 1.3 mg/m2 i.v. or s.c. on days 1, 4, 8, 11, 22, 25, 29 and 32 of cycles 1–4, and days 1, 8, 22 and 29 of cycles 5–9; melphalan 9 mg/m2 on days 1–4; prednisone p.o. 60 mg/m2 on days 1–4 of all cycles |
NDMM | NCT0181875251 |
| Carfilzomib | Phase III Addition of carfilzomib to dexamethasone once weekly versus twice weekly ORR, PFS and OS |
Carfilzomib once weekly: carfilzomib 20 mg/m2 i.v. on day 1 of cycle 1, then 70 mg/m2 on days 8 and 15 of cycle 1 and days 1, 8 and 15 of other cycles; dexamethasone 40 mg i.v. or orally on days 1, 8, 15 and 22 of cycles 1–9 and days 1, 8 and 15 of all other cycles Carfilzomib twice weekly: carfilzomib 20 mg/m2 i.v. on days 1 and 2 of cycle 1, then 27 mg/m2 on days 8, 9, 15 and 16 of cycle 1 and days 1, 2, 8, 9, 15 and 16 of other cycles; dexamethasone p.o. (same as other arm) |
RRMM | NCT0241287844 |
| Ixazomib | Phase III IRD versus RD PFS |
IRD: ixazomib 4 mg p.o. on days 1,8 and 15; lenalidomide 25 mg p.o. on days 1–21; and dexamethasone 40 mg p.o. on days 1, 8, 15 and 22 of 28-day cycles (until disease progression) RD: placebo p.o. on days 1, 8 and 15; lenalidomide and dexamethasone p.o. (same as other arm) on 28-day cycles (until disease progression) |
NDMM | NCT01850524145 |
| RRMM | NCT01564537146 | |||
| Ixazomib | Phase III Ixazomib versus placebo PFS |
Ixazomib 3 mg p.o. on days 1, 8 and 15 of cycles 1–4, then 3–4 mg on days 1, 8 and 15 of cycles 5–26 of 28-day cycles | NDMM, maintenance without aSCT | NCT02312258147 |
| NDMM, maintenance after aSCT | NCT02181413128 |
aSCT, autologous stem cell transplantation; CMP, carfilzomib, melphalan, prednisone; CRD, carfilzomib, lenalidomide, dexamethasone; IRD, ixazomib, lenalidomide, dexamethasone; i.v., intravenous; NDMM, newly diagnosed multiple myeloma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; p.o, by mouth; RD, lenalidomide, dexamethasone; RRMM, relapsed and/or refractory myeloma; s.c., subcutaneous; VMP, bortezomib, melphalan, prednisone; VRD, bortezomib, lenalidomide, dexamethasone.