Study: NCT01554852

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen
Description: Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4 \& 12-15 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen
Description: Days 1,8,15 (i.e. weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg hard capsules. Initially 100 mg daily PO for 3 weeks, increasing to 200 mg daily PO Days 1-4 and 12-15 - dexamethasone 40 mg daily PO The cycle is repeated every 21 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen
Description: Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1 \& 2, 8 \& 9, 15 \& 16 - carfilzomib 20\*/36 mg/m2\*\* IV (\*carfilzomib 20 mg/m2 is only administered on days 1 and 2 of cycle 1; \*\*carfilzomib will be dose capped at a body surface area of 2.2 m2) Days 1-21 - lenalidomide 25 mg daily PO Days 1-4, 8, 9 \& 15, 16 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen
Description: Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4 \& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen
Description: Days 1, 8, 15, 22 (weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg hard capsules; initially 50 mg daily PO for 4 weeks, increasing every 4 weeks by 50 mg increments to 200 mg daily PO Days 1-4 \& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen
Description: Days 1, 4, 8 \& 11 - bortezomib 1.3 mg/m2 SC or IV Days 1, 8, 15 - cyclophosphamide 500 mg PO Days 1-2, 4-5, 8-9 \& 11-12 - dexamethasone 20 mg daily PO This cycle is repeated every 21 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen
Description: Days 1, 4, 8 \& 11 - bortezomib 1.3 mg/m2 SC or IV Days 1, 8, 15 - cyclophosphamide 500 mg PO Days 1-2, 4-5, 8-9 \& 11-12 - dexamethasone 20 mg daily PO This cycle is repeated every 21 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance
Description: Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance
Description: Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance
Description: Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance
Description: Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: High dose melphalan therapy and autologous stem cell transplant (intensive pathway only)
Description: High dose melphalan therapy and autologous stem cell transplant to be given as per local practice