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

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ClinicalTrials.gov Identifier: NCT02541383
Recruitment Status : Recruiting
First Posted : September 4, 2015
Last Update Posted : June 2, 2016
Sponsor:
Collaborators:
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
Observation
Experimental: Arm B Part 2
daratumumab
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



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

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 ClinicalTrials.gov identifier (NCT number): NCT02541383


Contacts
Contact: Claire Mathiot, Dr 0033157276829 ifmsecretgene@outlook.fr

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Sponsors and Collaborators
Intergroupe Francophone du Myelome
HOVON - Dutch Haemato-Oncology Association
Janssen Research & Development, LLC
Investigators
Principal Investigator: Philippe Moreau, Pr CHU Nantes, France

Responsible Party: Intergroupe Francophone du Myelome
ClinicalTrials.gov 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
daratumumab

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