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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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ClinicalTrials.gov Identifier: NCT04975997
Recruitment Status : Recruiting
First Posted : July 26, 2021
Last Update Posted : June 2, 2023
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Dexamethasone Drug: Daratumumab Drug: Bortezomib Drug: Iberdomide Phase 3

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).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 864 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : June 23, 2022
Estimated Primary Completion Date : June 18, 2027
Estimated Study Completion Date : January 26, 2033

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Daratumumab in combination with Iberdomide and dexamethasone - Dose 1
Participants will receive oral iberdomide, subcutaneous daratumumab and oral dexamethasone.
 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
Other Name: DARZALEX FASPRO

Drug: Iberdomide
Oral Iberdomide 1.0mg on Days 1 to 21 of a 28-day cycle
Other Names:
  • CC-220
  • BMS-986382
Experimental: Daratumumab in combination with Iberdomide and dexamethasone - Dose 2 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
Other Name: DARZALEX FASPRO

Drug: Iberdomide
Oral Iberdomide 1.3mg on Days 1 to 21 of a 28-day cycle
Other Names:
  • CC-220
  • BMS-986382
Experimental: Daratumumab in combination with Iberdomide and dexamethasone - Dose 3 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
Other Name: DARZALEX FASPRO

Drug: Iberdomide
Oral Iberdomide 1.6mg on Days 1 to 21 of a 28-day cycle
Other Names:
  • CC-220
  • BMS-986382
Active Comparator: Daratumumab in combination with dexamethasone and bortezomib
Participants will receive subcutaneous daratumumab, bortezomib and oral dexamethasone
 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
Other Name: DARZALEX FASPRO

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.


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Up to approximately 5 years ]
    To compare the efficacy of iberdomide, daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, and dexamethasone (DVd) in terms of progression-free survival (PFS) in participants with relapsed or refractory multiple myeloma (RRMM).


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
    To evaluate clinical efficacy in terms of overall survival (OS) in participants with relapsed or refractory multiple myeloma (RRMM) treated with iberdomide, daratumumab, and dexamethasone (IberDd) compared to daratumumab, bortezomib, and dexamethasone (DVd).

  2. Minimal Residual Disease (MRD) negativity rate [ Time Frame: Up to approximately 5 years ]
    Proportion of participants who achieve complete response (CR) or better and are MRD negative (defined at a sensitivity of a minimum of 1 in 105 nucleated cells by next generation flow cytometry).

  3. Overall Response Rate (ORR) [ Time Frame: Up to approximately 5 years ]
    Calculated as percentage of participants who achieve best response of partial response (PR) or better according to the IMWG Uniform Response Criteria for multiple myeloma.

  4. Time to response (TTR) [ Time Frame: Up to approximately 5 years ]
    Time from randomization to the first documentation of response (PR or better).

  5. Duration of Response (DoR) [ Time Frame: Up to approximately 5 years ]
    Time from the first documentation of response (PR or better) to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.

  6. Time to Progression (TTP) [ Time Frame: Up to approximately 5 years ]
    The time from randomization to the first documented disease progression.

  7. Time to Next Treatment (TTNT) [ Time Frame: Up to approximately 5 years ]
    Time from randomization to the start of the next antimyeloma treatment.

  8. Progression-free Survival 2 (PFS2) [ Time Frame: Up to approximately 5 years ]
    Time from randomization to progression on the next anti-myeloma treatment or death due to any cause, whichever occurs first.

  9. Safety [ Time Frame: Up to approximately 5 years ]
    Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment.

  10. European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) [ Time Frame: Up to approximately 5 years ]
    Mean changes from baseline in subscale scores in subject-reported health related quality of life outcomes and multiple myeloma-related symptoms as measured by the EORTC QLQ-C30.

  11. European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) [ Time Frame: Up to approximately 5 years ]
    EORTC QLQ-MY20 is a 20-item myeloma module intended for use among participants varying in disease stage and treatment modality. Mean changes from baseline in subscale scores in subject-reported health related quality of life outcomes and multiple myeloma-related symptoms as measured by the EORTC QLQ- MY20.

  12. Recommended iberdomide dose for Stage 2 [ Time Frame: Up to approximately 1 year ]
  13. Area under the plasma concentration-time curve from time zero to tau (AUC(TAU)) [ Time Frame: Up to approximately 1 year ]
  14. Maximum plasma concentration (Cmax) [ Time Frame: Up to approximately 1 year ]
  15. Time to maximum plasma concentration (Tmax) [ Time Frame: Up to approximately 1 year ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Contacts and Locations
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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): NCT04975997


Contacts
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Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT # and Site #.

Locations
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Sponsors and Collaborators
Celgene
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT04975997    
Other Study ID Numbers: CC-220-MM-002
U1111-1260-2872 ( Other Identifier: UTN Number )
2020-000431-49 ( EudraCT Number )
First Posted: July 26, 2021    Key Record Dates
Last Update Posted: June 2, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene:
Iberdomide
CC-220
Daratumumab
Darzalex Faspro
Bortezomib
Velcade
 Dexamethasone
MM
Multiple Myeloma
RRMM
CELMoD
Cereblon Modulators
Additional relevant MeSH terms:
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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
Bortezomib
Daratumumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents