Use of Thalidomide, Lenalidomide, Carfilzomib, Bortezomib and Vorinostat in the Initial Treatment of Newly Diagnosed Multiple Myeloma Patients

Sponsor
University of Leeds
Study ID
NCT01554852
Phase
PHASE3
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen — DRUG
    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
  • Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen — DRUG
    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
  • Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen — DRUG
    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
  • Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen — DRUG
    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
  • Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen — DRUG
    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
  • Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen — DRUG
    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
  • Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance — DRUG
    Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days
  • Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance — DRUG
    Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days
  • High dose melphalan therapy and autologous stem cell transplant (intensive pathway only) — DRUG
    High dose melphalan therapy and autologous stem cell transplant to be given as per local practice

Study Details

The purpose of this study is to compare a standard chemotherapy regimen of cyclophosphamide, dexamethasone plus thalidomide with a newer regimen of cyclophosphamide, dexamethasone plus lenalidomide with or without carfilzomib. Patients who do not have the best response to their initial treatment may then also be given a combination of cyclophosphamide, dexamethasone plus bortezomib. Patients who are relatively fit may, on their doctor's advice, go on to receive more intensive chemotherapy, supported with a transplant of their own blood cells. This is standard treatment which patients may be offered anyway even if they didn't take part in this study. After maximal response has been achieved with the treatment described above, and as long as the myeloma has not got worse, patients will be treated with either long-term lenalidomide, lenalidomide with vorinostat, or receive no further treatment, with close observation.

Key Dates

Start date
May 31, 2010
Status verified
Jun 2018
Primary completion
Dec 31, 2021
Completion
Dec 31, 2022

Study Design

Enrollment
4,420 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Intensive pathway
    The intensive pathway is aimed at younger and fitter patients who will receive the standard dose of chemotherapy. The initial treatments will be followed by high-dose chemotherapy with a stem cell transplant which is generally standard practice. Participants receive one treatment from each following stage in intensive pathway, depending on what they are randomised to (Protocol v6.0): 1. Induction treatment: 1. CRD regimen - cyclophosphamide, lenalidomide, dexamethasone 2. CTD regimen - cyclophosphamide, thalidomide, dexamethasone 3. CCRD regimen - carfilzomib, cyclophosphamide, lenalidomide, dexamethasone 2. Consolidation treatment (depending on response to induction treatment): 1. VCD regimen - bortezomib, cyclosphosphamide, dexamethasone 2. No consolidation treatment 3. High-dose therapy and stem cell transplant 4. Maintenance treatment: 1. Lenalidomide maintenance 2. No maintenance 3. Lenalidomide plus vorinostat maintenance (Protocol v5.0 only)
  • Active Comparator: Non-intensive pathway
    The non-intensive pathway is aimed at participants who are not deemed suitable for the stem cell transplant, and will receive lower doses of some of the drugs. Interventions in each stage of non-intensive pathway (depending on what the participant has been randomised to) - from Protocol v6.0: 1. Induction treatment 1. CRDa regimen - cyclophosphamide, lenalidomide, dexamethasone attenuated 2. CTDa regimen - cyclophosphamide, thalidomide, dexamethasone attenuated 2. Consolidation treatment (depending on participant's response to induction treatment): 1. VCD regimen - bortezomib, cyclosphosphamide, dexamethasone 2. No consolidation treatment 3. Maintenance treatment 1. Lenalidomide maintenance 2. No maintenance 3. Lenalidomide plus vorinostat maintenance (\*for participants recruited under Protocol v5.0 only\*)

Primary Outcome Measure

Overall survival [ Time Frame: Time from initial randomisation to the trial death from any cause or last follow-up ]

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