IFM 2005-01: Velcade/Dexamethasone Versus Vincristine/Adriamycin (Doxorubicin)/Dexamethasone (VAD) for the Treatment of Patients With Multiple Myeloma

Etude Multicentrique Ouverte Randomisée de Phase III Comparant l'Association de VELCADE®-Dexaméthasone à la Chimiothérapie de Type VAD Pour le Traitement Des Patients Porteurs de Myélome Multiple de Novo Jusqu'à l'âge de 65 Ans

This is an open-label, multi-centre, randomised Phase III study, looking at a series of 480 patients up to the age of 65 with newly diagnosed multiple myeloma (MM) not previously treated. They will receive VAD or Velcade®/dexamethasone combination as induction treatment plus/minus (±) dexamethasone/cyclophosphamide/etoposide/cisplatin (DCEP) followed by autograft as first-line therapy, as the investigators try to compare the complete remission (CR) rate (with negative or positive immunofixation) at the end of their induction treatment.

After their written informed consent has been obtained and their eligibility verified, patients are randomised between 4 treatment arms: A1 VAD (4 cycles); A2 VAD (4 cycles) followed by DCEP (2 cycles); B1 Velcade® + dexamethasone (4 cycles); B2 Velcade® + dexamethasone (4 cycles) followed by DCEP (2 cycles) A1, A2, B1, B2 + autograft. Randomisation will be stratified on the basis of the initial b2 microglobulin level (> or < 3 mg/l) and the presence of chromosome 13 abnormalities identified by FISH analysis. VAD: Vincristine/Adriamycin/Dexamethasone; DCEP: Dexamethasone/Cyclophosphamide/ Etoposide/Cisplatin.

Inclusion Criteria:

• Recently diagnosed MM according to the criteria of the South West Oncology Group (SWOG)
• Not previously treated, apart from local radiotherapy, in the case of a threatening or incapacitating lesion, and/or a 4-day block of dexamethasone (40 mg/mL) in an emergency
• Stage II or III disease according to the Durie and Salmon classification or Stage I disease with symptomatic bone lesion
• < 65 years of age
• Ability to give signed informed consent
• Secretion of a measurable monoclonal spike (> 10 g/l in the serum or 0.2 g/24h in the urine)
• Negative pregnancy test at inclusion (if necessary)
• Absence of active infection. In the case of infection, appropriate antibiotic therapy must be administered and patients must have been apyretic for 48 hours before the start of treatment with VAD or Velcade®/dexamethasone

Exclusion Criteria:

• ECOG performance status > 2
• History of cancer (other than basal cell carcinoma or carcinoma of the cervix in situ)
• Life expectancy < 2 months
• Confirmed amyloidosis
• Positive HIV serology
• Serious psychiatric item in the history
• Renal failure requiring dialysis
• Uncontrolled diabetes, contra-indicating the use of corticosteroids
• Peripheral neuropathy National Cancer Institute (NCI) grade > 2 (Annex 5)
• Clinical signs of heart failure or coronary heart disease
• Bilirubin > 3 x normal
• Transaminases or gamma-glutamyl transpeptidase (GT) > 4 x normal
• Platelets < 50 x 10^9/l during the 15 days prior to inclusion
• Neutrophils < 0.75 x 10^9/l during the 15 days prior to inclusion
• Use of an investigational medicinal product during the 30 days prior to inclusion
• Known hypersensitivity to bortezomib, boron or mannitol