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

Summary

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.

Conditions

• Multiple Myeloma

Interventions

DRUG

Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen

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

DRUG

Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen

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

DRUG

Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen

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

DRUG

Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen

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

DRUG

Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen

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

DRUG

Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen

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

DRUG

Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance

Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days

DRUG

Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance

Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days

DRUG

High dose melphalan therapy and autologous stem cell transplant (intensive pathway only)

High dose melphalan therapy and autologous stem cell transplant to be given as per local practice

Sponsors & Collaborators

• Celgene

  collaborator INDUSTRY

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• Amgen

  collaborator INDUSTRY

• University of Leeds

  lead OTHER

Principal Investigators

• Graham Jackson · Freeman Health System

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-05-31

Primary Completion

2021-12-31

Completion

2022-12-31

Countries

• United Kingdom