Clinical trial NCT02541383: A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma
Official title: Study of Daratumumab in Combination With Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) in the First Line Treatment of Transplant Eligible Subjects With Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Untreated Multiple Myeloma
daratumumab
Lead sponsor: Intergroupe Francophone du Myelome
Sponsor class: NETWORK
Collaborators: name: HOVON - Dutch Haemato-Oncology Association
name: Janssen Research & Development, LLC
First posted: 2015-09-04
Enrollment: 1085
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: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Post-Consolidation Stringent Complete Response (sCR) Rate
timeFrame: At day 100 post Autologous Stem Cell Transplant (ASCT), up to 114 days post ASCT
measure: Progression Free Survival (PFS) Post Completion of Maintenance Therapy
timeFrame: 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).
Secondary outcomes:
measure: Progression Free Survival (PFS) From First Randomization up to the End of the Study
timeFrame: 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
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: BE-Antwerp-ZNA Stuivenberg
city: Brugge
country: Belgium
facility: AZ St Jan Brugge Oostende AV
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: UCL Saint-Luc
city: Bruxelles
country: Belgium
facility: UZ Brussel
city: Charleroi
country: Belgium
facility: GHDC
city: Gent
country: Belgium
facility: UZ Gent
city: La Louviere
country: Belgium
facility: CH Jolimont
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Liege
country: Belgium
facility: Domaine Universitaire du Sart Tilman
city: Roeselare
country: Belgium
facility: AZ Delta
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne
city: AMIENS Cedex 1
country: France
facility: CHU Amiens Sud
city: ANGERS Cedex 1
country: France
facility: CHRU-Hôpital du Bocage
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil Victor Dupouy
city: AVIGNON Cedex 9
country: France
facility: Centre Hospitalier H.Duffaut
city: Bayonne
country: France
facility: Centre hospitalier de la Côte Basque
city: BESANCON Cedex
country: France
facility: Hôpital Jean Minjoz
city: BOBIGNY Cedex
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Acquitaine
city: BOURG EN BRESSE Cedex
country: France
facility: Hôpital de Fleyriat
city: BREST Cedex
country: France
facility: CHRU Brest - Hôpital A. Morvan
city: CAEN Cedex
country: France
facility: CHU Caen - Côte de Nacre
city: Castelnau-le-lez
country: France
facility: Clinique du Parc
city: Cergy-pontoise
country: France
facility: CH René Dubos
city: Cesson-Sévigné
country: France
facility: Hôpital Privé Sévigné
city: Chalon-sur-Saône
country: France
facility: Centre Hospitalier William Morey
city: Chambery
country: France
facility: CH Chambéry
city: CLAMART Cedex
country: France
facility: Hôpital d'Instruction des Armées Percy
city: Clermont-ferrand
country: France
facility: CHU d'Estaing
city: CORBEIL-ESSONNES Cedex
country: France
facility: Centre Hospitalier Sud Francilien
city: Creteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHRU Dijon - Hôpital des Enfants
city: Dunkerque
country: France
facility: Centre Hospitalier Général
city: GRENOBLE Cedex 9
country: France
facility: CHRU Hôpital A. Michallon
city: LA ROCHE SUR YON Cedex 9
country: France
facility: CHD Vendée
city: Le Chesnay
country: France
facility: CHV André Mignot - Université de Versailles
city: Le Coudray
country: France
facility: CH de Chartres - Hôpital Louis Pasteur
city: LE MANS Cedex
country: France
facility: Centre Hospitalier
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: LILLE Cedex
country: France
facility: CHRU Hôpital Claude Huriez
city: Lille
country: France
facility: GH de l'Institut Catholique Saint Vincent
city: Limoges
country: France
facility: Centre Hospitalier Universitaire (CHU) de Limoges
city: Lorient
country: France
facility: Hôpital du Scorff
city: Lyon
country: France
facility: Centre Léon Bérard
city: MARSEILLE Cedex
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: CH Meaux
city: METZ Cedex 1
country: France
facility: Hôpital de Mercy (CHR Metz-Thionville)
city: MONTPELLIER Cedex
country: France
facility: Hopital Saint Eloi - CHU Montpellier
city: Mulhouse
country: France
facility: Hôpital E. Muller
city: Nantes Cedex 1
country: France
facility: CHRU Hôtel Dieu
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: NICE Cedex 3
country: France
facility: Clinique de l'Archet
city: NIMES Cedex 9
country: France
facility: CHU Carémeau
city: Orleans Cedex 2
country: France
facility: CH La Source
city: PARIS Cedex 10
country: France
facility: Hôpital Saint Louis
city: PARIS Cedex 12
country: France
facility: CHU Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: La Pitié
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 - Centre François Magendie
city: PIERRE-BENITE Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU Poitiers - Pôle régional de Cancérologie
city: PRINGY Cedex
country: France
facility: Ch Annecy Genevois
city: REIMS Cedex
country: France
facility: Hôpital Robert Debré
city: RENNES Cedex 9
country: France
facility: CHRU Hôpital de Pontchaillou
city: ROUEN Cedex 1
country: France
facility: Centre Henri Becquerel
city: Saint Priest-en-jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: SAINT QUENTIN Cedex
country: France
facility: Centre Hospitalier
city: Saint-brieuc
country: France
facility: Centre Hospitalier Yves Le Foll
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Strasbourg
country: France
facility: Strasbourg Oncologie Médicale
city: TOULOUSE Cedex 9
country: France
facility: Pôle IUCT Oncopole CHU
city: TOURS Cedex
country: France
facility: CHRU Hôpital Bretonneau
city: VANDOEUVRE LES NANCY Cedex
country: France
facility: CHRU Hôpitaux de Brabois
city: VANNES Cedex
country: France
facility: CHBA
city: Alkmaar
country: Netherlands
facility: MC Alkmaar
city: Amersfoort
country: Netherlands
facility: Meander MC
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: Vumc
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Breda
country: Netherlands
facility: Amphia Hospital Breda
city: Delft
country: Netherlands
facility: RdGG
city: Den Haag
country: Netherlands
facility: Haga zkh
city: Deventer
country: Netherlands
facility: Deventer zkh
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer zkh
city: Eindhoven
country: Netherlands
facility: Maxima MC
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: UMCG
city: Heerlen
country: Netherlands
facility: Atrium MC/Zuyderland MC
city: Hilversum
country: Netherlands
facility: Tergooiziekenhuizen, location Hilversum
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Leeuwarden
country: Netherlands
facility: MC Leeuwarden
city: Leiden
country: Netherlands
facility: LUMC
city: Maastricht
country: Netherlands
facility: MUMC
city: Nieuwegein
country: Netherlands
facility: Antonius zkh
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
city: Tilburg
country: Netherlands
facility: Elisabeth zkh
city: Utrecht
country: Netherlands
facility: UMCU
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: CHU Nantes, France
name: Philippe Moreau, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, Bene MC, Broijl A, Caillon H, Caillot D, Corre J, Delforge M, Dejoie T, Doyen C, Facon T, Sonntag C, Fontan J, Garderet L, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Lenain P, Macro M, Mathiot C, Orsini-Piocelle F, Perrot A, Stoppa AM, van de Donk NW, Wuilleme S, Zweegman S, Kolb B, Touzeau C, Roussel M, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Fermand JP, Escoffre-Barbe M, Eveillard JR, Garidi R, Ahmadi T, Zhuang S, Chiu C, Pei L, de Boer C, Smith E, Deraedt W, Kampfenkel T, Schecter J, Vermeulen J, Avet-Loiseau H, Sonneveld P. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019 Jul 6;394(10192):29-38. doi: 10.1016/S0140-6736(19)31240-1. Epub 2019 Jun 3.
citation: Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, Bene MC, Zweegman S, Caillon H, Caillot D, Corre J, Delforge M, Dejoie T, Doyen C, Facon T, Sonntag C, Fontan J, Mohty M, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Macro M, Orsini-Piocelle F, Roussel M, Stoppa AM, van de Donk NWCJ, Wuilleme S, Broijl A, Touzeau C, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Offner F, Escoffre-Barbe M, Eveillard JR, Garidi R, Ahmadi T, Krevvata M, Zhang K, de Boer C, Vara S, Kampfenkel T, Vanquickelberghe V, Vermeulen J, Avet-Loiseau H, Sonneveld P. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1378-1390. doi: 10.1016/S1470-2045(21)00428-9. Epub 2021 Sep 13.
citation: Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, Zweegman S, Caillon H, Caillot D, Avet-Loiseau H, Delforge M, Dejoie T, Facon T, Sonntag C, Fontan J, Mohty M, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Macro M, Orsini-Piocelle F, Roussel M, Schiano de Colella JM, van de Donk NW, Wuilleme S, Broijl A, Touzeau C, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Offner F, Escoffre-Barbe M, Eveillard JR, Garidi R, Hua W, Wang J, Tuozzo A, de Boer C, Rowe M, Vanquickelberghe V, Carson R, Vermeulen J, Corre J, Sonneveld P; Intergroupe Francophone du Myelome, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and the CASSIOPEIA Investigators. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. Lancet Oncol. 2024 Aug;25(8):1003-1014. doi: 10.1016/S1470-2045(24)00282-1. Epub 2024 Jun 15.
citation: Alberge JB, Kraeber-Bodere F, Jamet B, Touzeau C, Caillon H, Wuilleme S, Bene MC, Kampfenkel T, Sonneveld P, van Duin M, Avet-Loiseau H, Corre J, Magrangeas F, Carlier T, Bodet-Milin C, Cherel M, Moreau P, Minvielle S, Bailly C. Molecular Signature of 18F-FDG PET Biomarkers in Newly Diagnosed Multiple Myeloma Patients: A Genome-Wide Transcriptome Analysis from the CASSIOPET Study. J Nucl Med. 2022 Jul;63(7):1008-1013. doi: 10.2967/jnumed.121.262884. Epub 2022 Jan 27.
citation: Hulin C, Offner F, Moreau P, Roussel M, Belhadj K, Benboubker L, Caillot D, Facon T, Garderet L, Kuhnowski F, Stoppa AM, Kolb B, Tiab M, Jie KS, Westerman M, Lambert J, Pei L, Vanquickelberghe V, De Boer C, Vermeulen J, Kampfenkel T, Sonneveld P, Van de Donk NWCJ. Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab + bortezomib/thalidomide/dexamethasone in the phase 3 CASSIOPEIA study. Haematologica. 2021 Aug 1;106(8):2257-2260. doi: 10.3324/haematol.2020.261842. No abstract available.
citation: Roussel M, Moreau P, Hebraud B, Laribi K, Jaccard A, Dib M, Slama B, Dorvaux V, Royer B, Frenzel L, Zweegman S, Klein SK, Broijl A, Jie KS, Wang J, Vanquickelberghe V, de Boer C, Kampfenkel T, Gries KS, Fastenau J, Sonneveld P. Bortezomib, thalidomide, and dexamethasone with or without daratumumab for transplantation-eligible patients with newly diagnosed multiple myeloma (CASSIOPEIA): health-related quality of life outcomes of a randomised, open-label, phase 3 trial. Lancet Haematol. 2020 Dec;7(12):e874-e883. doi: 10.1016/S2352-3026(20)30356-2.