Efficacy Study Comparing Velcade Dexamethasone Thalidomide Versus Velcade Cyclophosphamide Dexamethasone as Induction Treatment in the Initial Management of Multiple Myeloma (IFM2013-04)
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT01971658
- Lead Sponsor
- Nantes University Hospital
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 358
Patients newly diagnosed with symptomatic Multiple Myeloma (MM) patient
-
- 18 ≤ age < 66 years
-
- Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2
-
- Patients must be eligible for Autologous Stem Cell Transplantation
-
- Patients must have measurable disease by serum M-protein ≥ 10 g/L and/or urine M-protein ≥200mg/day
-
- 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.
-
- 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
-
- 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.
-
- Patients must be capable of giving informed consent
-
- Patients must be affiliated with French social security system
-
- Asymptomatic Multiple myeloma
-
- Non-secretory Multiple myeloma
-
- Proven AL-amyloidosis
-
- Age ≥ 66 years old
-
- 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)
-
- Radiation therapy in the 2 weeks preceding randomization
-
- National Cancer Institute grade ≥ 2 peripheral neuropathy
-
- Haemoglobin < 8g/dL
-
- Absolute neutrophil count < 1,000 cells / µL, platelet count < 50,000 cells / µL
-
- Creatinine level > 170 µmol/L or requiring dialysis.
-
- Bilirubin, transaminases or GamaGT > 3 UNL (upper normal limit)
-
- Positive HIV serology, evidence of active Hepatitis B and C infection
-
- Severe active infection
-
- Inability to comply with an anti-thrombotic treatment regimen
-
- A personal medical history of severe psychiatric disease
-
- Uncontrolled diabetes contraindicating the use of high-dose dexamethasone
-
- Non-controlled or severe cardiovascular disease (including a myocardial infarction in the 6 months prior to recruitment)
-
- 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)
-
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD) Thalidomide® Arm A: 1. Induction therapy 4 cycles of VTD (21 days) Thalidomide® 100 mg/day Per Os Day1 to Day21 Velcade® 1.3 mg/m²/day Subcutaneous Day1, 4, 8 and 11 Dexamethasone 40 mg/day Per Os Day 1 to 4 and Day 9 to 12 2. Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and one week after the last dose of Thalidomide, stem cells have to be harvested VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD) Velcade® Arm A: 1. Induction therapy 4 cycles of VTD (21 days) Thalidomide® 100 mg/day Per Os Day1 to Day21 Velcade® 1.3 mg/m²/day Subcutaneous Day1, 4, 8 and 11 Dexamethasone 40 mg/day Per Os Day 1 to 4 and Day 9 to 12 2. Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and one week after the last dose of Thalidomide, stem cells have to be harvested VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD) Velcade® For arm B: 1. Induction therapy : 4 cycles of VCD (21 days) * Cyclophosphamide 500 mg/m²/day, Per Os Day 1, 8, 15 * Velcade® and Dexamethasone identical treatment to Arm A 2. Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and two weeks after the last dose of Cyclophosphamide, stem cells have to be harvested VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD) Cyclophosphamide For arm B: 1. Induction therapy : 4 cycles of VCD (21 days) * Cyclophosphamide 500 mg/m²/day, Per Os Day 1, 8, 15 * Velcade® and Dexamethasone identical treatment to Arm A 2. Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and two weeks after the last dose of Cyclophosphamide, stem cells have to be harvested VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD) Dexaméthasone Arm A: 1. Induction therapy 4 cycles of VTD (21 days) Thalidomide® 100 mg/day Per Os Day1 to Day21 Velcade® 1.3 mg/m²/day Subcutaneous Day1, 4, 8 and 11 Dexamethasone 40 mg/day Per Os Day 1 to 4 and Day 9 to 12 2. Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and one week after the last dose of Thalidomide, stem cells have to be harvested VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD) Dexaméthasone For arm B: 1. Induction therapy : 4 cycles of VCD (21 days) * Cyclophosphamide 500 mg/m²/day, Per Os Day 1, 8, 15 * Velcade® and Dexamethasone identical treatment to Arm A 2. Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and two weeks after the last dose of Cyclophosphamide, stem cells have to be harvested
- Primary Outcome Measures
Name Time Method Response assessment according to the criteria IMWG 15-17 month compare the Response assessment in both arms: the Very good partial remission rate (according to the criteria IMWG) achieved with four courses of VTD with that achieved with four courses of VCD
- Secondary Outcome Measures
Name Time Method Response assessment according to the criteria IMWG 15-17 month compare the Response assessment in both arms: Compare the following parameters after induction treatment with four courses of VTD or four courses of VCD the Partial remission rate (according to the criteria IMWG)
Number of Adverse Events 15-17 month To evaluate the Safety of induction therapy
Number of collected stem cell 17 month Number of death 17 month To evaluate Overall and Progression-Free Survival
Number of relapse according to the criteria IMWG 17 month Progression-Free Survival
Trial Locations
- Locations (62)
CHRU - Hôpital A.Michallon
🇫🇷Grenoble, France
Centre Hospitalier Argenteuil
🇫🇷Argenteuil, France
Hôpital Avicenne
🇫🇷Bobigny, France
CHU Caen Côte de Nacre
🇫🇷Caen, France
CH Le Mans
🇫🇷Le Mans, France
Centre Hospitalier de la Côte Basque
🇫🇷Bayonne, France
Hôpital d'instruction des armées Percy
🇫🇷Clamart, France
Centre Léon Bérard
🇫🇷Lyon, France
Centre Hospitalier de Meaux
🇫🇷Meaux, France
Centre hospitalier Pierre Oudot
🇫🇷Bourgoin Jallieu, France
Hôpital A.Morvan
🇫🇷Brest, France
Hopital E Muller
🇫🇷Mulhouse, France
CH René Dubos
🇫🇷Cergy-pontoise, France
CHU de Limoges
🇫🇷Limoges, France
Hôpitaux civils de Colmar
🇫🇷Colmar, France
CHU d'Estaing
🇫🇷Clermont-ferrand, France
Centre Hospitalier Général
🇫🇷Dunkerque, France
CHU Henri Mondor
🇫🇷Creteil, France
Hôpital Louis Pasteur
🇫🇷Le Coudray, France
Hopital Saint Vincent de Paul
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Hôpital Du Scorff
🇫🇷Lorient, France
Centre Jean Bernard
🇫🇷Le Mans, France
CHR Metz Thionville
🇫🇷Metz, France
Centre Hospitalier intercommunale Meulan les mureaux
🇫🇷Meulan, France
AP-HP Hôpital Necker
🇫🇷Paris, France
Groupe Hospitalo-Universitaire Carémeau
🇫🇷Nimes, France
CHU - Hôpital St-Antoine
🇫🇷Paris, France
Hôpital de l'Archet 1
🇫🇷Nice, France
CH Saint Jean
🇫🇷Perpignan, France
CHRU - Hôpital du Haut Lévêque
🇫🇷Pessac, France
Centre Hospitalier Lyon sud
🇫🇷Pierre Benite, France
CHRU - Hôpital Jean Bernard
🇫🇷Poitiers, France
Centre Hospitalier
🇫🇷Saint Quentin, France
Centre Hospitalier Yves le Foll
🇫🇷St Brieuc, France
Centre René Huguenin
🇫🇷St Cloud, France
Centre Henri Becquerel
🇫🇷Rouen, France
Centre hospitalier
🇫🇷ST Malo, France
Institut de Cancérologie de la Loire
🇫🇷St Priest-en-jarez, France
Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
CHRU - Hôpital Bretonneau
🇫🇷Tours, France
CHRU - Hôpitaux de Brabois
🇫🇷Vandoeuvre Les Nancy, France
CH Bretagne Atlantique Vannes et Auray
🇫🇷Vannes, France
Centre Hospitalier de la région d'Annecy
🇫🇷Annecy, Pringy, France
CHRU Hôpital Sud
🇫🇷Amiens, France
CHU Angers
🇫🇷Angers, France
Centre Hospitalier H.Duffaut
🇫🇷Avignon, France
CHRU de Besançon
🇫🇷Besançon, France
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
Centre Hospitalier William Morey
🇫🇷Chalon/saone, France
CHRU Dijon
🇫🇷Dijon, France
Centre hospitalier départemental Vendée
🇫🇷La Roche Sur Yon, France
CHRU - Hôpital Claude Huriez
🇫🇷Lille, France
Hôpital Cochin
🇫🇷Paris, France
Nantes University Hospital
🇫🇷Nantes, France
Hôpital Pitié-Salpétrière
🇫🇷Paris, France
Institut CURIE
🇫🇷Paris, France
Centre Hospitalier de PERIGUEUX
🇫🇷Perigueux, France
CHRU - Hôpital Purpan
🇫🇷Toulouse, France
CHRU - Hôpital de Pontchaillou
🇫🇷Rennes, France
Hôpital R.Debré
🇫🇷Reims, France
Centre Hospitalier Sud Francilien
🇫🇷Corbeil-essonnes, France