A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)

• ClinicalTrials.gov Identifier: NCT03989414
• Recruitment Status: Active, not recruiting
• First Posted: June 18, 2019
• Last Update Posted: May 6, 2024
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: June 14, 2019
• First Posted Date: June 18, 2019
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: September 30, 2019
• Estimated Primary Completion Date: November 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2022)

• Recommended Dose [ Time Frame: Up to approximately 3 years ]
• Recommended regimen as measured by dose-limiting toxicities [ Time Frame: Up to approximately 3 years ]
• Number of participants with Adverse Events (AEs) [ Time Frame: From first participant first visit until 28 days after the last subject discontinues study treatment, up to 5 years ]
• Overall response rate (ORR) [ Time Frame: Up to approximately 5 years ]

Original Primary Outcome Measures (submitted: June 14, 2019)

• Dose-limiting Toxicities (DLT) [ Time Frame: UP to approximately 2 years from enrollment ]
  Number of participants with DLTs in the first cycle of the treatment
• Adverse Events (AEs) [ Time Frame: From first subject first visit until 28 days after the last subject discontinues study treatment. ]
  Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment
• Overall response rate (ORR) [ Time Frame: UP to approximately 3 years from enrollment ]
  Defined as the proportion of subjects who achieve partial response (PR)or better according to the International Myeloma Working Group (IMWG) Uniform Response Criteria .

Current Secondary Outcome Measures (submitted: April 27, 2022)

• Time-to-response (TTR) [ Time Frame: Up to approximately 5 years ]
• Duration of response (DOR) [ Time Frame: Up to approximately 5 years ]
• Complete Response (CR) rate [ Time Frame: Up to approximately 5 years ]
• Very good partial response (VGPR) rate - Cohorts D and E [ Time Frame: Up to approximately 5 years ]

Original Secondary Outcome Measures (submitted: June 14, 2019)

• Time-to-response (TTR) [ Time Frame: UP to approximately 3 years from enrollment ]
  Time from first dose to the first documentation of response (PR or greater)
• Duration of response (DOR) [ Time Frame: Up to approximately 3 years from enrollment ]
  Time from the first documentation of response (PR or greater) to the first documentation of progressive disease (PD) or death
• Complete Response (CR) rate [ Time Frame: Up to approximately 3 years from enrollment ]
  Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria
• Very good partial response (VGPR) rate [ Time Frame: Up to approximately 3 years from enrollment ]
  Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
• Official Title: A Phase 1/2, Multicenter, Open-label, Study to Determine the Recommended Dose and Regimen, and Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Subjects With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
• Brief Summary: The purpose of this study is to evaluate the safety and preliminary efficacy of CC-92480 in combination with standard treatments.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: CC-92480
  Specified dose on specified days
  Other Names:

  • BMS-986348
  • mezigdomide
• Drug: Bortezomib
  Specified dose on specified days
• Drug: Dexamethasone
  Specified dose on specified days
• Drug: Daratumumab
  Specified dose on specified days
• Drug: Carfilzomib
  Specified dose on specified days
• Drug: Elotuzumab
  Specified dose on specified days
• Drug: Isatuximab
  Specified dose on specified days

Study Arms

• Experimental: Cohort A: CC-92480 with bortezomib and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Experimental: Cohort C: CC-92480 with carfilzomib and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Carfilzomib
• Experimental: Cohort H: CC-92480 with elotuzumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Elotuzumab
• Experimental: Cohort I: CC-92480 with isatuximab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Isatuximab
• Experimental: Cohort D: CC-92480 with bortezomib and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Experimental: Cohort F: CC-92480 with carfilzomib and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Carfilzomib
• Experimental: Cohort J: CC-92480 with elotuzumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Elotuzumab
• Experimental: Cohort K: CC-92480 with isatuximab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Isatuximab
• Experimental: Cohort G: CC-92480 with bortezomib and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Experimental: Subcohort B1: CC-92480 with daratumumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Subcohort B2: CC-92480 with daratumumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Subcohort B3: CC-92480 with daratumumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Subcohort E1: CC-92480 with daratumumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Subcohort E2: CC-92480 with daratumumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Subcohort E3: CC-92480 with daratumumab and dexamethasone
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 13, 2023): 424
• Original Estimated Enrollment (submitted: June 14, 2019): 238
• Estimated Study Completion Date: November 30, 2026
• Estimated Primary Completion Date: November 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2

For participants in Cohorts A, B, C, D, E, F, H, I, J, and K the following inclusions will also apply:

• Documented diagnosis of multiple myeloma (MM) and measurable disease
• Documented disease progression during or after their last antimyeloma regimen
• Achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen

Exclusion Criteria:

• Plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant amyloidosis
• Known central nervous system (CNS) involvement with myeloma
• Received immunosuppressive medication within the last 14 days of initiating study treatment
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment

Other protocol-defined inclusion/exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Denmark, France, Germany, Greece, Italy, Spain, United States

Administrative Information

• NCT Number: NCT03989414
• Other Study ID Numbers: CC-92480-MM-002; U1111-1233-5619 ( Other Identifier: WHO ); 2018-004767-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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

• Current Responsible Party: Celgene
• Original Responsible Party: Same as current
• Current Study Sponsor: Celgene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Celgene
• Verification Date: May 2024