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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02541383
Recruitment Status : Recruiting
First Posted : September 4, 2015
Last Update Posted : June 2, 2016
HOVON - Dutch Haemato-Oncology Association
Janssen Research & Development, LLC
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) Drug: Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab Drug: Daratumumab Phase 3

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  (Clinical Trial)
Estimated Enrollment : 1080 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2015
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2024

Arm Intervention/treatment
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 Name: 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 Name: Arm B Part 1

No Intervention: Arm A Part 2
Experimental: Arm B Part 2
Drug: Daratumumab
Daratumumab 16mg/kg every 8 weeks for 2 years
Other Name: Arm B Part 2

Primary Outcome Measures :
  1. stringent complete response (sCR) after consolidation therapy [ Time Frame: Up to 9 months ]
    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

  2. Progression free survival after maintenance therapy [ Time Frame: up to 60 months ]
    Time from the date of second randomization to either progressive disease (PD) or death

Secondary Outcome Measures :
  1. PFS (Progression-Free Survival) (from first randomization) [ Time Frame: Up to 60 months ]
    time from the initial randomization to either confirmed progressive disease (PD) or death

  2. Time to Progression (TTP) [ Time Frame: Up to 60 months ]
    Time from the initial randomization to confirmed progressive disease (PD) or death due to progressive disease

  3. proportion of Post ASCT (Autologous Stem Cell Transplantation) / consolidation CR rate [ Time Frame: Up to 9 months ]
    Proportion of participants who have achieved CR or sCR by the end of consolidation treatment

  4. proportion of Post ASCT/consolidation MRD (Minimal Residual Disease) negativation [ Time Frame: Up to 9 months ]
    proportion of participants who have achieved MRD (minimal residual disease) negative status by the end of consolidation

  5. proportion of Post induction sCR [ Time Frame: Up to 4 months ]
    proportion of participants who have achieved sCR (stringent complete response) prior to high-dose therapy/ASCT (autologous stem cell transplantation)

  6. PFS 2 (from first randomization) [ Time Frame: Up to 60 months ]
    time from initial randomization to subsequent progression on next-line of therapy after disease progression on study treatment

  7. OS (overall survival) (from first randomization) [ Time Frame: Up to 60 months ]
    time from initial randomization to death

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02541383

Contact: Claire Mathiot, Dr 0033157276829

  Hide Study Locations
BE-Antwerp-ZNA Stuivenberg Recruiting
Antwerp, Belgium
AZ St Jan Brugge Oostende AV Not yet recruiting
Brugge, Belgium
Institut Jules Bordet Recruiting
Bruxelles, Belgium
UCL Saint-Luc Recruiting
Bruxelles, Belgium
UZ Brussel Recruiting
Bruxelles, Belgium
GHDC Not yet recruiting
Charleroi, Belgium
UZ Gent Recruiting
Gent, Belgium
CH Jolimont Not yet recruiting
La Louviere, Belgium
University Hospital Leuven Not yet recruiting
Leuven, Belgium
CHR Citadelle Not yet recruiting
Liege, Belgium
Domaine Universitaire du Sart Tilman Recruiting
Liege, Belgium
CHU Vésale Not yet recruiting
Montigny Le Tilleul, Belgium
AZ Delta Not yet recruiting
Roeselare, Belgium
AZ Turnhout Recruiting
Turnhout, Belgium
UCL Mont-Godinne Recruiting
Yvoir, Belgium
CHU Amiens Sud Recruiting
AMIENS Cedex 1, France
CHRU-Hôpital du Bocage Recruiting
ANGERS Cedex 1, France
Centre Hospitalier d'Argenteuil Victor Dupouy Not yet recruiting
Argenteuil, France
Centre Hospitalier H.Duffaut Recruiting
AVIGNON Cedex 9, France
Centre hospitalier de la Côte Basque Recruiting
Bayonne, France
Hôpital Jean Minjoz Recruiting
BESANCON Cedex, France
Hôpital Avicenne Recruiting
BOBIGNY Cedex, France
Polyclinique Bordeaux Nord Acquitaine Recruiting
Bordeaux, France
Hôpital de Fleyriat Not yet recruiting
CHRU Brest - Hôpital A. Morvan Recruiting
BREST Cedex, France
CHU Caen - Côte de Nacre Recruiting
CAEN Cedex, France
Clinique du Parc Recruiting
Castelnau-le-lez, France
CH René Dubos Recruiting
Cergy-pontoise, France
Hôpital Privé Sévigné Recruiting
Cesson-Sévigné, France
Centre Hospitalier William Morey Recruiting
Chalons Sur Saone, France
CH Chambéry Recruiting
Chambery, France
Hôpital d'Instruction des Armées Percy Not yet recruiting
CLAMART Cedex, France
CHU d'Estaing Recruiting
Clermont-ferrand, France
Centre Hospitalier Sud Francilien Recruiting
CHU Henri Mondor Recruiting
Creteil, France
CHRU Dijon - Hôpital des Enfants Recruiting
Dijon, France
Centre Hospitalier Général Recruiting
Dunkerque, France
CHRU Hôpital A. Michallon Recruiting
GRENOBLE Cedex 9, France
CHD Vendée Recruiting
LA ROCHE SUR YON Cedex 9, France
CHV André Mignot - Université de Versailles Recruiting
Le Chesnay, France
CH de Chartres - Hôpital Louis Pasteur Not yet recruiting
Le Coudray, France
Centre Hospitalier Recruiting
LE MANS Cedex, France
Clinique Victor Hugo Recruiting
Le Mans, France
CHRU Hôpital Claude Huriez Recruiting
LILLE Cedex, France
GH de l'Institut Catholique Saint Vincent Recruiting
Lille, France
Centre Hospitalier Universitaire (CHU) de Limoges Recruiting
Limoges, France
Hôpital du Scorff Recruiting
Lorient, France
Centre Léon Bérard Not yet recruiting
Lyon, France
Institut Paoli Calmettes Recruiting
MARSEILLE Cedex, France
CH Meaux Recruiting
Meaux, France
Hôpital de Mercy (CHR Metz-Thionville) Recruiting
METZ Cedex 1, France
Hopital Saint Eloi - CHU Montpellier Recruiting
Hôpital E. Muller Recruiting
Mulhouse, France
CHRU Hôtel Dieu Recruiting
Nantes Cedex 1, France
Clinique de l'Archet Recruiting
NICE Cedex 3, France
CHU Carémeau Recruiting
NIMES Cedex 9, France
CH La Source Recruiting
Orleans Cedex 2, France
Hôpital Saint Louis Recruiting
PARIS Cedex 10, France
CHU Hôpital Saint Antoine Recruiting
PARIS Cedex 12, France
Hôpital Cochin Not yet recruiting
Paris, France
Hôpital Necker Recruiting
Paris, France
Institut Curie Recruiting
Paris, France
La Pitié Recruiting
Paris, France
Centre Hospitalier de Perigueux Not yet recruiting
Perigueux, France
CH Saint Jean Not yet recruiting
Perpignan, France
CHRU - Hôpital du Haut Lévêque - Centre François Magendie Recruiting
Pessac, France
Centre Hospitalier Lyon Sud Recruiting
CHU Poitiers - Pôle régional de Cancérologie Recruiting
Poitiers, France
Ch Annecy Genevois Recruiting
PRINGY Cedex, France
Hôpital Robert Debré Recruiting
REIMS Cedex, France
CHRU Hôpital de Pontchaillou Recruiting
RENNES Cedex 9, France
Centre Henri Becquerel Recruiting
ROUEN Cedex 1, France
Institut de Cancérologie Lucien Neuwirth Recruiting
Saint Priest-en-jarez, France
Centre Hospitalier Recruiting
Centre Hospitalier Yves Le Foll Recruiting
Saint-brieuc, France
CHU Strasbourg Recruiting
Strasbourg, France
Strasbourg Oncologie Médicale Recruiting
Strasbourg, France
Pôle IUCT Oncopole CHU Recruiting
TOULOUSE Cedex 9, France
CHRU Hôpital Bretonneau Recruiting
TOURS Cedex, France
CHRU Hôpitaux de Brabois Recruiting
CHBA Recruiting
VANNES Cedex, France
UH Luxembourg Not yet recruiting
Luxembourg, Luxembourg
MC Alkmaar Recruiting
Alkmaar, Netherlands
Meander MC Not yet recruiting
Amersfoort, Netherlands
AMC Not yet recruiting
Amsterdam, Netherlands
OLVG Not yet recruiting
Amsterdam, Netherlands
Vumc Recruiting
Amsterdam, Netherlands
Ziekenhuis Rijnstate Not yet recruiting
Arnhem, Netherlands
Amphia Hospital Breda Not yet recruiting
Breda, Netherlands
RdGG Not yet recruiting
Delft, Netherlands
Haga zkh Recruiting
Den Haag, Netherlands
Deventer zkh Not yet recruiting
Deventer, Netherlands
Albert Schweitzer zkh Recruiting
Dordrecht, Netherlands
Maxima MC Not yet recruiting
Eindhoven, Netherlands
Medisch Spectrum Twente Not yet recruiting
Enschede, Netherlands
UMCG Not yet recruiting
Groningen, Netherlands
Atrium MC/Zuyderland MC Not yet recruiting
Heerlen, Netherlands
Spaarne Gasthuis Not yet recruiting
Hoofddorp, Netherlands
MC Leeuwarden Not yet recruiting
Leeuwarden, Netherlands
LUMC Not yet recruiting
Leiden, Netherlands
MUMC Not yet recruiting
Maastricht, Netherlands
Antonius zkh Not yet recruiting
Nieuwegein, Netherlands
Canisius-Wilhelmina Nijmegen ZH Not yet recruiting
Nijmegen, Netherlands
Radboudumc Not yet recruiting
Nijmegen, Netherlands
Erasmus MC Recruiting
Rotterdam, Netherlands
Maasstad Ziekenhuis Recruiting
Rotterdam, Netherlands
Elisabeth zkh Not yet recruiting
Tilburg, Netherlands
UMCU Not yet recruiting
Utrecht, Netherlands
Isala Klinieken Not yet recruiting
Zwolle, Netherlands
Sponsors and Collaborators
Intergroupe Francophone du Myelome
HOVON - Dutch Haemato-Oncology Association
Janssen Research & Development, LLC
Principal Investigator: Philippe Moreau, Pr CHU Nantes, France

Responsible Party: Intergroupe Francophone du Myelome Identifier: NCT02541383     History of Changes
Other Study ID Numbers: IFM 2015-01
HO131 ( Other Identifier: HOVON )
54767414MMY3006 ( Other Identifier: J&J )
2014-004781-15 ( EudraCT Number )
First Posted: September 4, 2015    Key Record Dates
Last Update Posted: June 2, 2016
Last Verified: May 2016

Keywords provided by Intergroupe Francophone du Myelome:
Untreated Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists