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

• ClinicalTrials.gov Identifier: NCT02541383
• Recruitment Status: Unknown
• First Posted: September 4, 2015
• Last Update Posted: December 7, 2020
• Sponsor: Intergroupe Francophone du Myelome
• Collaborators: HOVON - Dutch Haemato-Oncology Association; Janssen Research & Development, LLC
• Information provided by (Responsible Party): Intergroupe Francophone du Myelome

Tracking Information

• First Submitted Date: June 24, 2015
• First Posted Date: September 4, 2015
• Last Update Posted Date: December 7, 2020
• Actual Study Start Date: September 2015
• Actual Primary Completion Date: August 27, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2015)

• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 1, 2015)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

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
  Other Name: Arm A Part 1
• 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
• Drug: Daratumumab
  Daratumumab 16mg/kg every 8 weeks for 2 years
  Other Name: Arm B Part 2

Study Arms

• Arm A Part 1
  Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)
  Intervention: Drug: Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)
• Experimental: Arm B Part 1
  Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) plus daratumumab
  Intervention: Drug: Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab
• No Intervention: Arm A Part 2
  Observation
• Experimental: Arm B Part 2
  daratumumab
  Intervention: Drug: Daratumumab

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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: August 23, 2018): 1085
• Original Estimated Enrollment (submitted: September 1, 2015): 1080
• Estimated Study Completion Date: June 19, 2023
• Actual Primary Completion Date: August 27, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Netherlands
• Removed Location Countries: Luxembourg

Administrative Information

• NCT Number: NCT02541383
• Other Study ID Numbers: IFM 2015-01; HO131 ( Other Identifier: HOVON ); 54767414MMY3006 ( Other Identifier: J&J ); 2014-004781-15 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Intergroupe Francophone du Myelome
• Original Responsible Party: Same as current
• Current Study Sponsor: Intergroupe Francophone du Myelome
• Original Study Sponsor: Same as current

Collaborators

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

Investigators

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

• PRS Account: Intergroupe Francophone du Myelome
• Verification Date: December 2020