Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM)

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Full Title:
A Phase 3, Two-Stage, Randomized, Multicenter, Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Subjects With Relapsed or Refractory Multiple Myeloma (RRMM)
Myeloma stage or condition:
Multiple Myeloma
Study phase:
Phase 3
Summary/Purpose:
This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in combination with dexamethasone and daratumumab (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM).
Detailed Description:
This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in combination with dexamethasone and daratumumab (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM). Approximately 200 patients randomized in stage 1 to one of three iberdomide dose levels of 1, 1.3, or 1.6 mg in combination with daratumumab and dexamethasone (Treatment Arms A1, A2, or A3), or to the DVd comparator arm (Treatment Arm B). In Stage 2 of the study, approximately 664 additional subjects will be randomized 1:1 between 2 treatment arms: * Approximately 332 subjects will be randomized to receive Treatment Arm A (IberDd) * Approximately 332 subjects will be randomized to receive Treatment Arm B (DVd) Participants in both treatment arms will continue to receive treatment until confirmed progressive disease (PD), unacceptable toxicity or withdrawal of consent. To ensure accuracy and completeness of the primary endpoint assessment of progression-free survival (PFS), participants who permanently discontinue study treatment for any reason, other than confirmed PD or withdrawal of consent, will continue to be followed for disease assessment. The study will be conducted in compliance with International Council for Harmonisation (ICH) and Good Clinical Practices (GCPs).
Treatments:
Drug : Dexamethasone

Oral dexamethasone 40mg on days 1, 8, 15, 22 of a 28-day cycle

Drug : Daratumumab

Subcutaneous Daratumumab 1800mg on Days 1, 8, 15 and 22 for Cycles 1 to 2, on Days 1 and 15 for Cycles 3 to 6, and then on Day 1 for Cycle 7 of a 28-day cycle

Drug : Bortezomib

Subcutaneous Bortezomib 1.3 mg/m2 on Days 1, 4, 8 and 11 of each 21-day cycle for a total of 8 cycles.

Drug : Iberdomide

Oral Iberdomide 1.0mg on Days 1 to 21 of a 28-day cycle

Drug : Iberdomide

Oral Iberdomide 1.3mg on Days 1 to 21 of a 28-day cycle

Drug : Iberdomide

Oral Iberdomide 1.6mg on Days 1 to 21 of a 28-day cycle

Study Arms:
Experimental : Daratumumab in combination with Iberdomide and dexamethasone - Dose 1
Participants will receive oral iberdomide, subcutaneous daratumumab and oral dexamethasone.
Experimental : Daratumumab in combination with Iberdomide and dexamethasone - Dose 2
Experimental : Daratumumab in combination with Iberdomide and dexamethasone - Dose 3
Active Comparator : Daratumumab in combination with dexamethasone and bortezomib
Participants will receive subcutaneous daratumumab, bortezomib and oral dexamethasone
Study Type:
Interventional
Study Design:
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: None
Recruitment status:
Recruiting
Eligibility criteria:
eria * Documented diagnosis of multiple myeloma (MM) and measurable disease. * Received 1 to 2 prior lines of anti-myeloma therapy. * Must have documented disease progression during or after their last anti-myeloma regimen. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2. Exclusion Criteria * Any condition that confounds the ability to interpret data from the study. * Has plasma cell leukemia, Waldenstrom's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis. * Known central nervous system involvement with MM. * Prior therapy with iberdomide. * Other protocol-defined Inclusion/Exclusion criteria apply.
Locations / Centres:

Local Institution - 111, Calgary, Alberta – Completed

Local Institution - 103, Edmonton, Alberta – Completed

BC Cancer Agency, Fraser Valley Center, Surrey, British Columbia – Recruiting

Local Institution - 104, Saint John, New Brunswick – Completed

Memorial University of NewfoundlandDr. H Bliss Murphy Cancer Center, St John's, Newfoundland and Labrador – Recruiting

Queen Elizabeth Ii Health Sciences Centre, Halifax, Nova Scotia – Recruiting

Local Institution - 109, Ottawa, Quebec – Completed

Local Institution - 107, Saskatoon, Saskatchewan – Completed

CHU de Quebec-Universite Laval, Quebec, – Recruiting

Contacts:
Name: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
Phone: 855-907-3286
Email: [email protected]
Publications:
???
First posted:
Not available
Actual start date:
2022-06-23
Last updated:
2024-11-16
Estimated enrollment:
864
Estimated completion date:
2032-06-25
Estimated primary completion date:
2026-03-18
Condition:
Multiple Myeloma
Gender:
All
Ages:
18 Years-
Accepts healthy volunteers:
Not available
Listed location countries:
Not available
NCT number:
NCT04975997
Other study ID numbers:
CC-220-MM-002
Has Data monitoring committee:
Yes
U.S. FDA-regulated product:
Yes
IPD Sharing Statement :
???
Responsible party:
Sponsor
Study sponsor:
lead_sponsor
Celgene
Industry
Collaborators:
???
Investigators:
Bristol-Myers Squibb Bristol-Myers Squibb
Protocol Registration and Results System:
???
Verification date:
2024-11-01