A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma

Multiple Myeloma Clinical Trial

— Cassiopeia  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02541383
• Other study ID #: IFM 2015-01
• Secondary ID: HO13154767414MMY
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: June 19, 2023

Study information

• Verified date: December 2020
• Source: Intergroupe Francophone du Myelome
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1085
• Est. completion date: June 19, 2023
• Est. primary completion date: August 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)
Part 1: 4 Cycles of Bortezomib,Thalidomide and Dexamethasone induction therapy, followed by Autologous Stem Cell Transplantation, followed by 2 cycles of Bortezomib, Thalidomide and Dexamethasone consolidation
• Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab
Part 1: 4 Cycles of Bortezomib, Thalidomide and Dexamethasone plus daratumumab 16mg/kg induction therapy, followed by Autologous Stem Cell Transplantation, followed by 2 cycles of Bortezomib, Thalidomide and Dexamethasone plus daratumumab 16 mg/kg consolidation
• Daratumumab
Daratumumab 16mg/kg every 8 weeks for 2 years

Locations

Country	Name	City	State
Belgium	BE-Antwerp-ZNA Stuivenberg	Antwerp
Belgium	AZ St Jan Brugge Oostende AV	Brugge
Belgium	Institut Jules Bordet	Bruxelles
Belgium	UCL Saint-Luc	Bruxelles
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	AZ Delta	Roeselare
Belgium	AZ Turnhout	Turnhout
Belgium	UCL Mont-Godinne	Yvoir
France	CHU Amiens Sud	AMIENS Cedex 1
France	CHRU-Hôpital du Bocage	ANGERS 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	CH Chambéry	Chambery
France	Hôpital d'Instruction des Armées Percy	CLAMART Cedex
France	CHU d'Estaing	Clermont-ferrand
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	CHD Vendée	LA ROCHE SUR YON Cedex 9
France	CHV André Mignot - Université de Versailles	Le Chesnay
France	CH de Chartres - Hôpital Louis Pasteur	Le Coudray
France	Clinique Victor Hugo	Le Mans
France	Centre Hospitalier	LE MANS Cedex
France	GH de l'Institut Catholique Saint Vincent	Lille
France	CHRU Hôpital Claude Huriez	LILLE Cedex
France	Centre Hospitalier Universitaire (CHU) de Limoges	Limoges
France	Hôpital du Scorff	Lorient
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmettes	MARSEILLE Cedex
France	CH Meaux	Meaux
France	Hôpital de Mercy (CHR Metz-Thionville)	METZ Cedex 1
France	Hopital Saint Eloi - CHU Montpellier	MONTPELLIER Cedex
France	Hôpital E. Muller	Mulhouse
France	Centre Catherine de Sienne	Nantes
France	CHRU Hôtel Dieu	Nantes Cedex 1
France	Clinique de l'Archet	NICE Cedex 3
France	CHU Carémeau	NIMES Cedex 9
France	CH La Source	Orleans Cedex 2
France	Hôpital Cochin	Paris
France	Hôpital Necker	Paris
France	Institut Curie	Paris
France	La Pitié	Paris
France	Hôpital Saint Louis	PARIS Cedex 10
France	CHU Hôpital Saint Antoine	PARIS Cedex 12
France	Centre Hospitalier de Perigueux	Perigueux
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	SAINT QUENTIN Cedex
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
Netherlands	MC Alkmaar	Alkmaar
Netherlands	Meander MC	Amersfoort
Netherlands	AMC	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	Vumc	Amsterdam
Netherlands	Ziekenhuis Rijnstate	Arnhem
Netherlands	Amphia Hospital Breda	Breda
Netherlands	RdGG	Delft
Netherlands	Haga zkh	Den Haag
Netherlands	Deventer zkh	Deventer
Netherlands	Albert Schweitzer zkh	Dordrecht
Netherlands	Maxima MC	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	UMCG	Groningen
Netherlands	Atrium MC/Zuyderland MC	Heerlen
Netherlands	Tergooiziekenhuizen, location Hilversum	Hilversum
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	MC Leeuwarden	Leeuwarden
Netherlands	LUMC	Leiden
Netherlands	MUMC	Maastricht
Netherlands	Antonius zkh	Nieuwegein
Netherlands	Radboudumc	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Maasstad Ziekenhuis	Rotterdam
Netherlands	Elisabeth zkh	Tilburg
Netherlands	UMCU	Utrecht
Netherlands	Isala Klinieken	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Intergroupe Francophone du Myelome	HOVON - Dutch Haemato-Oncology Association, Janssen Research & Development, LLC

Countries where clinical trial is conducted

Belgium,  France,  Netherlands, 

References & Publications (1)

Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, Béné 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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	stringent complete response (sCR) after consolidation therapy	sCR is defined by achieving CR (complete response) in addition to having a normal serum FLC (Free Light Chain) ratio and absence of clonal cells in bone marrow	Up to 9 months
Primary	Progression free survival after maintenance therapy	Time from the date of second randomization to either progressive disease (PD) or death	up to 60 months
Secondary	PFS (Progression-Free Survival) (from first randomization)	time from the initial randomization to either confirmed progressive disease (PD) or death	Up to 60 months
Secondary	Time to Progression (TTP)	Time from the initial randomization to confirmed progressive disease (PD) or death due to progressive disease	Up to 60 months
Secondary	proportion of Post ASCT (Autologous Stem Cell Transplantation) / consolidation CR rate	Proportion of participants who have achieved CR or sCR by the end of consolidation treatment	Up to 9 months
Secondary	proportion of Post ASCT/consolidation MRD (Minimal Residual Disease) negativation	proportion of participants who have achieved MRD (minimal residual disease) negative status by the end of consolidation	Up to 9 months
Secondary	proportion of Post induction sCR	proportion of participants who have achieved sCR (stringent complete response) prior to high-dose therapy/ASCT (autologous stem cell transplantation)	Up to 4 months
Secondary	PFS 2 (from first randomization)	time from initial randomization to subsequent progression on next-line of therapy after disease progression on study treatment	Up to 60 months
Secondary	OS (overall survival) (from first randomization)	time from initial randomization to death	Up to 60 months

External Links

•   FDA approval
•   positive study part II results