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

March 26, 2025 updated by: Intergroupe Francophone du Myelome

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1085

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium
        • BE-Antwerp-ZNA Stuivenberg
      • Brugge, Belgium
        • AZ St Jan Brugge Oostende AV
      • Bruxelles, Belgium
        • Institut Jules Bordet
      • Bruxelles, Belgium
        • UCL Saint-Luc
      • Bruxelles, Belgium
        • UZ Brussel
      • Charleroi, Belgium
        • GHdC
      • Gent, Belgium
        • UZ Gent
      • La Louviere, Belgium
        • CH Jolimont
      • Leuven, Belgium
        • University Hospital Leuven
      • Liege, Belgium
        • Domaine Universitaire du Sart Tilman
      • Roeselare, Belgium
        • AZ Delta
      • Turnhout, Belgium
        • AZ Turnhout
      • Yvoir, Belgium
        • UCL Mont-Godinne
  • France
      • AMIENS Cedex 1, France
        • Chu Amiens Sud
      • ANGERS Cedex 1, France
        • CHRU-Hôpital du Bocage
      • AVIGNON Cedex 9, France
        • Centre Hospitalier H.Duffaut
      • Argenteuil, France
        • Centre Hospitalier d'Argenteuil Victor Dupouy
      • BESANCON Cedex, France
        • Hopital Jean Minjoz
      • BOBIGNY Cedex, France
        • Hôpital Avicenne
      • BOURG EN BRESSE Cedex, France
        • Hôpital de Fleyriat
      • BREST Cedex, France
        • CHRU Brest - Hôpital A. Morvan
      • Bayonne, France
        • Centre Hospitalier de la Cote Basque
      • Bordeaux, France
        • Polyclinique Bordeaux Nord Acquitaine
      • CAEN Cedex, France
        • CHU Caen - Côte de Nacre
      • CLAMART Cedex, France
        • Hopital D'Instruction Des Armees Percy
      • CORBEIL-ESSONNES Cedex, France
        • Centre Hospitalier Sud Francilien
      • Castelnau-le-lez, France
        • Clinique du Parc
      • Cergy-pontoise, France
        • CH René Dubos
      • Cesson-Sévigné, France
        • Hôpital privé Sévigné
      • Chalon-sur-Saône, France, 71100
        • Centre Hospitalier William Morey
      • Chambery, France
        • CH Chambery
      • Clermont-ferrand, France
        • CHU d'Estaing
      • Creteil, France
        • CHU Henri Mondor
      • Dijon, France
        • CHRU Dijon - Hôpital des Enfants
      • Dunkerque, France
        • Centre Hospitalier Général
      • GRENOBLE Cedex 9, France
        • CHRU Hôpital A. Michallon
      • LA ROCHE SUR YON Cedex 9, France
        • CHD Vendee
      • LE MANS Cedex, France
        • Centre Hospitalier
      • LILLE Cedex, France
        • CHRU Hôpital Claude Huriez
      • Le Chesnay, France
        • CHV André Mignot - Université de Versailles
      • Le Coudray, France
        • CH de Chartres - Hôpital Louis Pasteur
      • Le Mans, France
        • Clinique Victor Hugo
      • Lille, France
        • GH de l'Institut Catholique Saint Vincent
      • Limoges, France
        • Centre Hospitalier Universitaire (CHU) de Limoges
      • Lorient, France
        • Hôpital du Scorff
      • Lyon, France
        • Centre Léon Bérard
      • MARSEILLE Cedex, France
        • Institut Paoli Calmettes
      • METZ Cedex 1, France
        • Hôpital de Mercy (CHR Metz-Thionville)
      • MONTPELLIER Cedex, France
        • Hopital Saint Eloi - CHU Montpellier
      • Meaux, France
        • CH Meaux
      • Mulhouse, France
        • Hôpital E. Muller
      • NICE Cedex 3, France
        • Clinique de l'Archet
      • NIMES Cedex 9, France
        • CHU Caremeau
      • Nantes, France, 44202
        • Centre Catherine de Sienne
      • Nantes Cedex 1, France
        • CHRU Hôtel Dieu
      • Orleans Cedex 2, France
        • CH La Source
      • PARIS Cedex 10, France
        • Hopital Saint Louis
      • PARIS Cedex 12, France
        • CHU Hopital Saint Antoine
      • PIERRE-BENITE Cedex, France
        • Centre Hospitalier Lyon Sud
      • PRINGY Cedex, France
        • Ch Annecy Genevois
      • Paris, France
        • Hopital Cochin
      • Paris, France
        • Hôpital Necker
      • Paris, France
        • Institut Curie
      • Paris, France
        • La Pitié
      • Perigueux, France
        • Centre Hospitalier de Perigueux
      • Perpignan, France
        • CH Saint Jean
      • Pessac, France
        • CHRU - Hôpital du Haut Lévêque - Centre François Magendie
      • Poitiers, France
        • CHU Poitiers - Pôle régional de Cancérologie
      • REIMS Cedex, France
        • Hôpital Robert Debré
      • RENNES Cedex 9, France
        • CHRU Hopital de Pontchaillou
      • ROUEN Cedex 1, France
        • Centre Henri Becquerel
      • SAINT QUENTIN Cedex, France
        • Centre Hospitalier
      • Saint Priest-en-jarez, France
        • Institut de Cancérologie Lucien Neuwirth
      • Saint-brieuc, France
        • Centre hospitalier Yves Le Foll
      • Strasbourg, France
        • CHU Strasbourg
      • Strasbourg, France
        • Strasbourg Oncologie Médicale
      • TOULOUSE Cedex 9, France
        • Pôle IUCT Oncopole CHU
      • TOURS Cedex, France
        • CHRU Hôpital Bretonneau
      • VANDOEUVRE LES NANCY Cedex, France
        • CHRU Hôpitaux de Brabois
      • VANNES Cedex, France
        • CHBA
  • Netherlands
      • Alkmaar, Netherlands
        • MC Alkmaar
      • Amersfoort, Netherlands
        • Meander MC
      • Amsterdam, Netherlands
        • AMC
      • Amsterdam, Netherlands
        • OLVG
      • Amsterdam, Netherlands
        • VUmc
      • Arnhem, Netherlands
        • Ziekenhuis Rijnstate
      • Breda, Netherlands
        • Amphia Hospital Breda
      • Delft, Netherlands
        • RdGG
      • Den Haag, Netherlands, 2545 CH
        • Haga zkh
      • Deventer, Netherlands
        • Deventer zkh
      • Dordrecht, Netherlands
        • Albert Schweitzer zkh
      • Eindhoven, Netherlands
        • Máxima MC
      • Enschede, Netherlands
        • Medisch Spectrum Twente
      • Groningen, Netherlands
        • UMCG
      • Heerlen, Netherlands
        • Atrium MC/Zuyderland MC
      • Hilversum, Netherlands, 1201 DA
        • Tergooiziekenhuizen, location Hilversum
      • Hoofddorp, Netherlands
        • Spaarne Gasthuis
      • Leeuwarden, Netherlands
        • MC Leeuwarden
      • Leiden, Netherlands
        • LUMC
      • Maastricht, Netherlands
        • MUMC
      • Nieuwegein, Netherlands
        • Antonius zkh
      • Nijmegen, Netherlands
        • Radboudumc
      • Rotterdam, Netherlands
        • Maasstad Ziekenhuis
      • Rotterdam, Netherlands
        • Erasmus MC
      • Tilburg, Netherlands
        • Elisabeth zkh
      • Utrecht, Netherlands
        • UMCU
      • Zwolle, Netherlands
        • Isala Klinieken

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Arm A Part 1
Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)
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
Other Names:
  • Arm A Part 1
Experimental: Arm B Part 1
Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) plus daratumumab
Drug: 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
Other Names:
  • Arm B Part 1
No Intervention: Arm A Part 2
Observation
Experimental: Arm B Part 2
daratumumab
Drug: Daratumumab
Daratumumab 16mg/kg every 8 weeks for 2 years
Other Names:
  • Arm B Part 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-Consolidation Stringent Complete Response (sCR) Rate
Time Frame: 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.
At day 100 post Autologous Stem Cell Transplant (ASCT), up to 114 days post ASCT
Progression Free Survival (PFS) Post Completion of Maintenance Therapy
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) From First Randomization up to the End of the Study
Time Frame: 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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intergroupe Francophone du Myelome

Collaborators

Janssen Research & Development, LLC
HOVON - Dutch Haemato-Oncology Association

Investigators

  • Principal Investigator: Philippe Moreau, Pr, CHU Nantes, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Actual)

August 27, 2020

Study Completion (Actual)

September 1, 2023

Study Registration Dates

First Submitted

June 24, 2015

First Submitted That Met QC Criteria

September 1, 2015

First Posted (Estimated)

September 4, 2015

Study Record Updates

Last Update Posted (Actual)

April 13, 2025

Last Update Submitted That Met QC Criteria

March 26, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFM 2015-01
  • HO131 (Other Identifier: HOVON)
  • 54767414MMY3006 (Other Identifier: J&J)
  • 2014-004781-15 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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