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

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: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD); Drug: Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab; Drug: Daratumumab

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

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
    • Hôpital 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 Côte Basque
  • Bordeaux, France
    • Polyclinique Bordeaux Nord Acquitaine
  • CAEN Cedex, France
    • CHU Caen - Côte de Nacre
  • CLAMART Cedex, France
    • Hôpital d'Instruction des Armées 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 General
  • 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
    • Hôpital 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
    • Hopital Robert Debre
  • 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
    • Maxima 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

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

How is the study designed?

Design Details

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

Number of Arms

4

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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS (Progression-Free Survival) (from first randomization)	time from the initial randomization to either confirmed progressive disease (PD) or death	Up to 60 months
Time to Progression (TTP)	Time from the initial randomization to confirmed progressive disease (PD) or death due to progressive disease	Up to 60 months
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
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
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
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
OS (overall survival) (from first randomization)	time from initial randomization to death	Up to 60 months

Collaborators and Investigators

• 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

General Publications

• 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. Erratum In: Lancet. 2019 Jun 14;:
• 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.
• 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.
• 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.
• 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.

Helpful Links

• FDA approval
• positive study part II results

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): August 27, 2020
• Study Completion (Anticipated): June 19, 2023

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (Estimate): September 4, 2015

Study Record Updates

• Last Update Posted (Actual): December 7, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: daratumumab; Untreated Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Thalidomide; Daratumumab; Bortezomib; Antibodies, Monoclonal
• 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