Clinical trial NCT01971658: Efficacy Study Comparing Velcade Dexamethasone Thalidomide Versus Velcade Cyclophosphamide Dexamethasone as Induction Treatment in the Initial Management of Multiple Myeloma (IFM2013-04)
Official title: A PHASE III STUDY OF VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD) VERSUS VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD) AS AN INDUCTION TREATMENT PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANTATION IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA."
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Newly Diagnosed
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2013-10-29
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III, multicenter, prospective with a clinical benefit, open-label and randomized study to compare two different treatments : Velcade (Bortezomib) Thalidomide Dexamethasone (VTD) versus Velcade (Bortezomib) Cyclophosphamide Dexamethasone (VCD) as an Induction Treatment prior to Autologous Stem Cell Transplantation in patients with Newly Diagnosed Multiple Myeloma.

Eligible patients will be randomized into 2 treatment arms. Each patient will receive 4 consecutive 21 day cycles of an induction treatment with either VTD or VCD.

Detailed description: The patient population will consist of adult men and women who have a confirmed diagnosis of Multiple Myeloma and who meet eligibility criteria. They will be recruited from among the patients consulting in an investigating centre's haematology service for newly diagnosed, symptomatic, untreated multiple myeloma.

in each treatment arm there will be :

1. Induction therapy : 4 cycles of VTD (21 days)or VCD
2. Systematic stem cell harvest after cycle 3

Eligibility criteria: Inclusion Criteria:

Patients newly diagnosed with symptomatic Multiple Myeloma (MM) patient

1. - 18 ≤ age \< 66 years
2. - Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2
3. - Patients must be eligible for Autologous Stem Cell Transplantation
4. - Patients must have measurable disease by serum M-protein ≥ 10 g/L and/or urine M-protein ≥200mg/day
5. - Female patients of child-bearing potential (FCBP):

   * Must agree to have medically supervised pregnancy tests prior to starting study and every 21 days, including 4 weeks after the end of study treatment. This applies even if the patient practices complete and continued sexual abstinence.
   * Must agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy.
6. - Male Patients:

   * Must agree to use a condom during sexual contact with a FCBP, throughout study drug therapy, during any dose interruption and for one week after discontinuation of study therapy
   * Must agree to not donate semen during study drug therapy and for one week after discontinuation of study therapy
7. - All patients must:

   * Agree to abstain from donating blood while taking study drug therapy and for one week after discontinuation of study drug therapy
   * Agree not to share study medication with another person.
8. - Patients must be capable of giving informed consent
9. - Patients must be affiliated with French social security system

Exclusion Criteria:

1. - Asymptomatic Multiple myeloma
2. - Non-secretory Multiple myeloma
3. - Proven AL-amyloidosis
4. - Age ≥ 66 years old
5. - Prior or current systemic therapy for Multiple myeloma, including steroids (except for emergency use of a 4-day block of dexamethasone before randomization, maximum total dose allowed 160 mg)
6. - Radiation therapy in the 2 weeks preceding randomization
7. - National Cancer Institute grade ≥ 2 peripheral neuropathy
8. - Haemoglobin \< 8g/dL
9. - Absolute neutrophil count \< 1,000 cells / µL, platelet count \< 50,000 cells / µL
10. - Creatinine level \> 170 µmol/L or requiring dialysis.
11. - Bilirubin, transaminases or GamaGT \> 3 UNL (upper normal limit)
12. - Positive HIV serology, evidence of active Hepatitis B and C infection
13. - Severe active infection
14. - Inability to comply with an anti-thrombotic treatment regimen
15. - A personal medical history of severe psychiatric disease
16. - Uncontrolled diabetes contraindicating the use of high-dose dexamethasone
17. - Non-controlled or severe cardiovascular disease (including a myocardial infarction in the 6 months prior to recruitment)
18. - A personal medical history of cancer unless the patient has been without relapse after treatment discontinuation \> or = 5 years (except for basocellular skin cancer or in situ cervical cancer)
19. - Use of any investigational drug in the 30 days preceding randomization

22 - Pregnant or lactating women. 23 - Adults under juridical protection 24 - Known or suspected hypersensitivity to any of the study therapies or excipients 25 - Necessity of vaccination for yellow fever or with any other live vaccines

Primary outcomes:
measure: Response assessment according to the criteria IMWG
timeFrame: 15-17 month
Secondary outcomes:
measure: Response assessment according to the criteria IMWG
timeFrame: 15 - 17 month
measure: Number of Adverse Events
timeFrame: 15-17 month
measure: Number of collected stem cell
timeFrame: 17 month
measure: Number of death
timeFrame: 17 month
measure: Response assessment according to the criteria IMWG
timeFrame: 15-17 month
measure: Number of relapse according to the criteria IMWG
timeFrame: 17 month
Other outcomes:
measure: Comparison of three techniques for the quantification of urinary monoclonal components in patients with Newly Diagnosed Multiple Myeloma.
timeFrame: 17 month
Locations:
city: Annecy
country: France
facility: Centre Hospitalier de la région d'Annecy
state: Pringy
city: Amiens
country: France
facility: CHRU Hôpital Sud
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: Centre Hospitalier Argenteuil
city: Avignon
country: France
facility: Centre Hospitalier H.Duffaut
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Besançon
country: France
facility: CHRU de Besançon
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Bourgoin Jallieu
country: France
facility: Centre hospitalier Pierre Oudot
city: Brest
country: France
facility: Hôpital A.Morvan
city: Caen
country: France
facility: CHU Caen Côte de Nacre
city: Cergy-pontoise
country: France
facility: CH René Dubos
city: Chalon/saone
country: France
facility: Centre Hospitalier William Morey
city: Clamart
country: France
facility: Hôpital d'instruction des armées Percy
city: Clermont-ferrand
country: France
facility: CHU d'Estaing
city: Colmar
country: France
facility: Hôpitaux civils de Colmar
city: Corbeil-essonnes
country: France
facility: Centre Hospitalier Sud Francilien
city: Creteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHRU Dijon
city: Dunkerque
country: France
facility: Centre Hospitalier Général
city: Grenoble
country: France
facility: CHRU - Hôpital A.Michallon
city: La Roche Sur Yon
country: France
facility: Centre hospitalier départemental Vendée
city: Le Coudray
country: France
facility: Hôpital Louis Pasteur
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: Hopital Saint Vincent de Paul
city: Lille
country: France
facility: CHRU - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU de Limoges
city: Lorient
country: France
facility: Hôpital Du Scorff
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Metz
country: France
facility: CHR Metz Thionville
city: Meulan
country: France
facility: Centre Hospitalier intercommunale Meulan les mureaux
city: Mulhouse
country: France
facility: Hopital E Muller
city: Nantes
country: France
facility: Nantes University Hospital
city: Nice
country: France
facility: Hôpital de l'Archet 1
city: Nimes
country: France
facility: Groupe Hospitalo-Universitaire Carémeau
city: PARIS cedex 12
country: France
facility: CHU - Hôpital St-Antoine
city: Paris
country: France
facility: Institut CURIE
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: CHU - Hôpital St-Antoine
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: AP-HP Hôpital Necker
city: Perigueux
country: France
facility: Centre Hospitalier de PERIGUEUX
city: Perpignan
country: France
facility: CH Saint Jean
city: Pessac
country: France
facility: CHRU - Hôpital du Haut Lévêque
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon sud
city: Poitiers
country: France
facility: CHRU - Hôpital Jean Bernard
city: Reims
country: France
facility: Hôpital R.Debré
city: Rennes
country: France
facility: CHRU - Hôpital de Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Quentin
country: France
facility: Centre Hospitalier
city: St Brieuc
country: France
facility: Centre Hospitalier Yves le Foll
city: St Cloud
country: France
facility: Centre René Huguenin
city: ST Malo
country: France
facility: Centre hospitalier
city: St Priest-en-jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: CHRU - Hôpital Purpan
city: Tours
country: France
facility: CHRU - Hôpital Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: CHRU - Hôpitaux de Brabois
city: Vannes
country: France
facility: CH Bretagne Atlantique Vannes et Auray
Study officials:
affiliation: Nantes University Hospital
name: Philippe MOREAU
role: PRINCIPAL_INVESTIGATOR
References: