A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02541383
- Lead Sponsor
- Intergroupe Francophone du Myelome
- Brief Summary
The purpose of this study is to evaluate if the addition of daratumumab to Bortezomib, Thalidomide and Dexamethasone will increase the stringent complete response rate after consolidation therapy and increase the progression free survival after daratumumab maintenance therapy in transplant eligible participants with previously untreated Multiple Myeloma.
- Detailed Description
This is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 2-arm (2 treatment groups), multicenter study of daratumumab in participants diagnosed with previously untreated Multiple Myeloma who are eligible for high dose chemotherapy and autologous stem cell transplantation (transplantation of own bone marrow). Participants will be randomized (assigned by chance) to one of 2 treatment groups to either receive daratumumab plus bortezomib, thalidomide and dexamethasone or bortezomib, thalidomide and dexamethasone for induction (before transplantation) and consolidation (after transplantation) treatment. All responders will then be re-randomized (assigned by chance) to one of 2 treatment groups to receive maintenance treatment with daratumumab only or observation (no treatment). The study will include a 28-Day Screening Phase, a Treatment Phase of 6 treatment cycles (each cycle is 4 weeks in duration for total period of 30 weeks), and a Follow up Phase of 2 years. The total duration for each participant in the study will be approximately 138 weeks. The end of the study will occur approximately 5 years after the last participant is randomized in the second phase of the study. Disease assessments will be performed every 4 weeks in the first phase of the study and then every 8 weeks in the second phase of the study. Safety will be monitored throughout the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1085
- Diagnosis of previously untreated multiple myeloma (MM)
- Have a confirmed diagnosis and eligible for high dose chemotherapy and autologous stem cell transplantation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1 or 2
- previous treatment for Multiple Myeloma
- Primary amyloidosis, Plasma Cell Leukemia or Smoldering Multiple Myeloma
- Prior or concurrent exposure to systemic therapy or SCT (Stem Cell Transplantation) for any plasma cell dyscrasia, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment, or received an investigational drug or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1
- history of malignancy (other than Multiple Myeloma) within 10 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
- known chronic obstructive pulmonary disease (COPD) or moderate to severe asthma
- any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Part 1 Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) Arm B Part 1 Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) plus daratumumab Arm B Part 2 Daratumumab daratumumab
- Primary Outcome Measures
Name Time Method Post-Consolidation Stringent Complete Response (sCR) Rate At day 100 post Autologous Stem Cell Transplant (ASCT), up to 114 days post ASCT Post-consolidation sCR rate is defined as the percentage of ITT subjects who achieved or maintained sCR status within 30 days of Day 100 post Autologous Stem Cell Transplant (ASCT). The sCR status is assessed using the computerized algorithm according to IMWG response criteria, and must be achieved on or prior to start of subsequent therapies. Subjects must not die or progress by Day 100 post ASCT.
According to the IMWG consensus recommendations for multiple myeloma treatment response criteria from 2006, the stringent complete response (sCR) was defined by a negative immunofixation on the serum and urine, and a disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow, plus normal free-light chain ratio and the absence of clonal bone marrow plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.Progression Free Survival (PFS) Post Completion of Maintenance Therapy From the date of second randomization to either progressive disease or death which ever occurred first, with a median follow-up time of 35.4 months (cut-off for analysis was 26 months after the last rando 2 date). Progression Free Survival (PFS) post completion of maintenance therapy is defined as the duration from the date of second randomization to either progressive disease (according to the IMWG criteria specified in the protocol), or death, whichever occurs first (=all these considered as events) at the completion of Maintenance therapy.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) From First Randomization up to the End of the Study From the date of first randomization to either progressive disease or death which ever occurred first, with a median follow-up time of 80.1 months at the end of the study Progression Free Survival (PFS) is defined as the duration from the date of first randomization to either progressive disease (according to the IMWG criteria specified in the protocol), or death, whichever occurs first (=all these considered as events) at the end of the study
Trial Locations
- Locations (106)
Centre Léon Bérard
🇫🇷Lyon, France
AZ St Jan Brugge Oostende AV
🇧🇪Brugge, Belgium
UZ Brussel
🇧🇪Bruxelles, Belgium
GHDC
🇧🇪Charleroi, Belgium
UZ Gent
🇧🇪Gent, Belgium
CH Jolimont
🇧🇪La Louviere, Belgium
University Hospital Leuven
🇧🇪Leuven, Belgium
Domaine Universitaire du Sart Tilman
🇧🇪Liege, Belgium
UCL Mont-Godinne
🇧🇪Yvoir, Belgium
CHRU-Hôpital du Bocage
🇫🇷ANGERS Cedex 1, France
CHU Amiens Sud
🇫🇷AMIENS Cedex 1, France
Centre Hospitalier d'Argenteuil Victor Dupouy
🇫🇷Argenteuil, France
Centre Hospitalier H.Duffaut
🇫🇷AVIGNON Cedex 9, France
Centre hospitalier de la Côte Basque
🇫🇷Bayonne, France
Hôpital Jean Minjoz
🇫🇷BESANCON Cedex, France
Hôpital Avicenne
🇫🇷BOBIGNY Cedex, France
Polyclinique Bordeaux Nord Acquitaine
🇫🇷Bordeaux, France
Hôpital de Fleyriat
🇫🇷BOURG EN BRESSE Cedex, France
CHRU Brest - Hôpital A. Morvan
🇫🇷BREST Cedex, France
CHU Caen - Côte de Nacre
🇫🇷CAEN Cedex, France
Clinique du Parc
🇫🇷Castelnau-le-lez, France
CH René Dubos
🇫🇷Cergy-pontoise, France
Hôpital Privé Sévigné
🇫🇷Cesson-Sévigné, France
Centre Hospitalier William Morey
🇫🇷Chalon-sur-Saône, France
CHU d'Estaing
🇫🇷Clermont-ferrand, France
CH Chambéry
🇫🇷Chambery, France
Hôpital d'Instruction des Armées Percy
🇫🇷CLAMART Cedex, France
Centre Hospitalier Sud Francilien
🇫🇷CORBEIL-ESSONNES Cedex, France
CHU Henri Mondor
🇫🇷Creteil, France
CHRU Dijon - Hôpital des Enfants
🇫🇷Dijon, France
Centre Hospitalier Général
🇫🇷Dunkerque, France
CHRU Hôpital A. Michallon
🇫🇷GRENOBLE Cedex 9, France
CHV André Mignot - Université de Versailles
🇫🇷Le Chesnay, France
CH de Chartres - Hôpital Louis Pasteur
🇫🇷Le Coudray, France
CHD Vendée
🇫🇷LA ROCHE SUR YON Cedex 9, France
Centre Hospitalier
🇫🇷SAINT QUENTIN Cedex, France
CHRU Hôpital Claude Huriez
🇫🇷LILLE Cedex, France
GH de l'Institut Catholique Saint Vincent
🇫🇷Lille, France
Centre Hospitalier Universitaire (CHU) de Limoges
🇫🇷Limoges, France
Hôpital du Scorff
🇫🇷Lorient, France
Institut Paoli Calmettes
🇫🇷MARSEILLE Cedex, France
CH Meaux
🇫🇷Meaux, France
Hopital Saint Eloi - CHU Montpellier
🇫🇷MONTPELLIER Cedex, France
Hôpital de Mercy (CHR Metz-Thionville)
🇫🇷METZ Cedex 1, France
Hôpital E. Muller
🇫🇷Mulhouse, France
Centre Catherine de Sienne
🇫🇷Nantes, France
Clinique de l'Archet
🇫🇷NICE Cedex 3, France
CHRU Hôtel Dieu
🇫🇷Nantes Cedex 1, France
CH La Source
🇫🇷Orleans Cedex 2, France
Hôpital Saint Louis
🇫🇷PARIS Cedex 10, France
CHU Hôpital Saint Antoine
🇫🇷PARIS Cedex 12, France
Hôpital Cochin
🇫🇷Paris, France
Centre Hospitalier de Perigueux
🇫🇷Perigueux, France
Institut Curie
🇫🇷Paris, France
CH Saint Jean
🇫🇷Perpignan, France
CHRU - Hôpital du Haut Lévêque - Centre François Magendie
🇫🇷Pessac, France
Centre Hospitalier Lyon Sud
🇫🇷PIERRE-BENITE Cedex, France
CHU Poitiers - Pôle régional de Cancérologie
🇫🇷Poitiers, France
Ch Annecy Genevois
🇫🇷PRINGY Cedex, France
Hôpital Robert Debré
🇫🇷REIMS Cedex, France
CHRU Hôpital de Pontchaillou
🇫🇷RENNES Cedex 9, France
Centre Henri Becquerel
🇫🇷ROUEN Cedex 1, France
Institut de Cancérologie Lucien Neuwirth
🇫🇷Saint Priest-en-jarez, France
Centre Hospitalier Yves Le Foll
🇫🇷Saint-brieuc, France
CHU Strasbourg
🇫🇷Strasbourg, France
Strasbourg Oncologie Médicale
🇫🇷Strasbourg, France
Pôle IUCT Oncopole CHU
🇫🇷TOULOUSE Cedex 9, France
CHRU Hôpital Bretonneau
🇫🇷TOURS Cedex, France
CHRU Hôpitaux de Brabois
🇫🇷VANDOEUVRE LES NANCY Cedex, France
CHBA
🇫🇷VANNES Cedex, France
AMC
🇳🇱Amsterdam, Netherlands
OLVG
🇳🇱Amsterdam, Netherlands
Amphia Hospital Breda
🇳🇱Breda, Netherlands
RdGG
🇳🇱Delft, Netherlands
UMCG
🇳🇱Groningen, Netherlands
LUMC
🇳🇱Leiden, Netherlands
Spaarne Gasthuis
🇳🇱Hoofddorp, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Maasstad Ziekenhuis
🇳🇱Rotterdam, Netherlands
Elisabeth zkh
🇳🇱Tilburg, Netherlands
Isala Klinieken
🇳🇱Zwolle, Netherlands
CHU Carémeau
🇫🇷NIMES Cedex 9, France
Hôpital Necker
🇫🇷Paris, France
La Pitié
🇫🇷Paris, France
MC Leeuwarden
🇳🇱Leeuwarden, Netherlands
UMCU
🇳🇱Utrecht, Netherlands
Vumc
🇳🇱Amsterdam, Netherlands
Ziekenhuis Rijnstate
🇳🇱Arnhem, Netherlands
Haga zkh
🇳🇱Den Haag, Netherlands
Deventer zkh
🇳🇱Deventer, Netherlands
Atrium MC/Zuyderland MC
🇳🇱Heerlen, Netherlands
Antonius zkh
🇳🇱Nieuwegein, Netherlands
Clinique Victor Hugo
🇫🇷Le Mans, France
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
BE-Antwerp-ZNA Stuivenberg
🇧🇪Antwerp, Belgium
UCL Saint-Luc
🇧🇪Bruxelles, Belgium
AZ Turnhout
🇧🇪Turnhout, Belgium
Albert Schweitzer zkh
🇳🇱Dordrecht, Netherlands
Maxima MC
🇳🇱Eindhoven, Netherlands
Tergooiziekenhuizen, location Hilversum
🇳🇱Hilversum, Netherlands
MC Alkmaar
🇳🇱Alkmaar, Netherlands
Meander MC
🇳🇱Amersfoort, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
MUMC
🇳🇱Maastricht, Netherlands