Table 2.
Dosing schedule for RCyBorD induction and each randomisation pathway
| Trial registration—induction (each cycle = 21 days) | ||
| Treatment (route) | Induction—all participants (starting dose) | Days |
| Bortezomib (SC) | 1.3 mg/m2 | 1, 8, 15 |
| Cyclophosphamide (PO) | 500 mg | 1, 8 |
| Lenalidomide (PO) | 25 mg | 1–14 |
| Dexamethasone (PO) | 40 mg | 1, 8, 15 |
| Isatuximab pre-randomisation 1 (each cycle = 28 days) | ||
| Treatment (route) | R1 pathway participants only (starting dose) | Days |
| Isatuximab (IV) | 10 mg/kg | 1, 8, 15 and 22 cycle 1 then days 1 and 15 from cycle two onwards |
| Randomisation 1: Isatuximab maintenance (each cycle = 28 days) | ||
| Treatment (route) | Isatuximab (days) | “Stop Isatuximab” |
| Isatuximab (IV) | 10 mg/kg (day 1 only) | None |
| Randomisation 2: MRD-positive treatment escalation pathway | |
| Treatment arm 1 (control): Lenalidomide (R) maintenance (each cycle = 28 days) | |
| Treatment (route) | Starting dose (days) |
| Lenalidomide (PO) | 10 mg/kg* (1–21) |
| Treatment arm 2: RBorD consolidation+R maintenance | ||
| Treatment (route) | Consolidation, starting dose (days) (each cycle = 21 days, 4 cycles) |
Maintenance, starting dose (days) (each cycle = 28 days) |
| Bortezomib (SC) | 1.3 mg/m2 (1, 8, 15) | NA |
| Lenalidomide (PO) | 15 mg* (1–14) | 10 mg* (1–21) |
| Dexamethasone (PO) | 20 mg (1, 8, 15) | NA |
| Treatment arm 3: RISa maintenance | |
| Treatment (route) | Maintenance, starting dose (days) (each cycle = 28 days) |
| Lenalidomide (PO) | 10 mg* (day 1–21) |
| Isatuximab (IV) | 10 mg/kg (1, 8, 15 and 22 cycle 1 then days 1 and 15 from cycle 2 onwards) |
| Treatment arm 4: RBorIsaD+RIsa | ||
| Treatment (route) | Consolidation, starting dose (days) (each cycle = 21 days, 4 cycles) |
Maintenance, starting dose (days) (each cycle = 28 days) |
| Bortezomib (SC) | 1.3 mg/m2 (1, 8, 15) | NA |
| Lenalidomide (PO) | 15 mg* (1–14) | 10 mg* (1–21) |
| Isatuximab (IV) | 10 mg/kg (1, 8, 15 cycle 1 then days 1 and 8 cycle 2, then days 1 and 15 cycle 3 onwards) | 10 mg/kg (1 and 15) |
| Dexamethasone (PO) | 20 mg (1, 8, 15) | NA |
| Randomisation 3: High risk treatment pathway | ||
| Treatment arm 1: RBorD consolidation and R maintenance | ||
| Treatment | Consolidation, starting dose (days) (each cycle = 21 days, 4 cycles) |
Maintenance, starting dose (days) (each cycle = 28 days) |
| Bortezomib (SC) | 1.3 mg/m2 (1, 8, 15) | NA |
| Lenalidomide (PO) | 15 mg* (1–14) | 10 mg* (1–21) |
| Dexamethasone (PO) | 20 mg (1, 8, 15) | NA |
| Treatment arm 2: RBorIsaD consolidation+RIsa maintenance | ||
| Treatment | Consolidation, starting dose (days) (each cycle = 21 days) |
Maintenance, starting dose (days) (each cycle = 28 days) |
| Bortezomib (SC) | 1.3 mg/m2 (1, 8, 15) | NA |
| Lenalidomide (PO) | 15 mg* (1–14) | 10 mg* (1–21) |
| Isatuximab (IV) | 10 mg/kg (1, 8, 15 cycle 1 then days 1 and 8 cycle 2, then days 1 and 15 cycle 3 onwards) | 10 mg/kg (1 and 15) |
| Dexamethasone (PO) | 20 mg (1, 8, 15) | NA |
*Or final dose administrated at the end of induction or consolidation treatment if lower.
IV, Intravenous; MRD, minimal residual disease; NA, not applicable; PO, By mouth; SC, Sub-cutaneous.