Multiple Myeloma
Conditions
Keywords
Iberdomide, CC-220, Daratumumab, Darzalex Faspro, Bortezomib, Velcade, Dexamethasone, MM, Multiple Myeloma, RRMM, CELMoD, Cereblon Modulators
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).
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).
Interventions
DRUGDexamethasone
Oral dexamethasone 40mg on days 1, 8, 15, 22 of a 28-day cycle
DRUGDaratumumab
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
DRUGBortezomib
Subcutaneous Bortezomib 1.3 mg/m2 on Days 1, 4, 8 and 11 of each 21-day cycle for a total of 8 cycles.
DRUGIberdomide
Oral Iberdomide 1.0mg on Days 1 to 21 of a 28-day cycle
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to approximately 5 years | To compare the efficacy of iberdomide (also known as BMS-986382), daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM) in terms of progression free survival (PFS). |
| Minimal Residual Disease (MRD) negative Complete Response (CR) at any time | Up to approximately 5 years | To compare the efficacy of iberdomide (also known as BMS-986382), daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM) in terms of minimal residual disease (MRD) negative complete response (CR) at any time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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). |
| Sustainability of Minimal Residual Disease (MRD) negativity | Up to approximately 5 years | To evaluate the sustainability of minimal residual disease (MRD) negativity. |
| Overall Response Rate (ORR) | 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. |
| Time to response (TTR) | Up to approximately 5 years | Time from randomization to the first documentation of response (PR or better). |
| Duration of Response (DoR) | 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. |
| Time to Progression (TTP) | Up to approximately 5 years | The time from randomization to the first documented disease progression. |
| Time to Next Treatment (TTNT) | Up to approximately 5 years | Time from randomization to the start of the next antimyeloma treatment. |
| Progression-free Survival 2 (PFS2) | 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. |
| Safety | Up to approximately 5 years | Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment. |
| European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) | 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. |
| European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) | 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. |
| Recommended iberdomide dose for Stage 2 | Up to approximately 1 year | — |
| Area under the plasma concentration-time curve from time zero to tau (AUC(TAU)) | Up to approximately 1 year | — |
| Maximum plasma concentration (Cmax) | Up to approximately 1 year | — |
| Time to maximum plasma concentration (Tmax) | Up to approximately 1 year | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed