A 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)
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT03989414 Recruiting June 18, 2019 October 2, 2020

study description
Brief Summary

This is an open-label, multicenter, Phase 1/2 study to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D), and to evaluate the safety and preliminary efficacy of CC-92480 in combination with standard treatments.

Condition or Disease: Multiple Myeloma
Intervention/treatment: Drug: CC-92480
Drug: Bortezomib
Drug: Dexamethasone
Drug: Daratumumab
Drug: Carfilzomib
Phase: Phase 1/Phase 2
Detailed Description

N/A


study design
Study Type: Interventional
Estimated Enrollment : 384 participants
Intervention Model : Parallel Assignment
Masking: None (Open Label) ()
Primary Purpose: Treatment
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)
Actual Study Start Date: September 2019
Estimated Primary Completion Date: September 2023
Estimated Study Completion Date: January 2025

Arms and interventions
Arm Intervention/treatment
Experimental: CC-92480 in combination with bortezomib and dexamethasone
Subjects in cohorts A, D and G will receive following: Oral CC-92480 at specified cohort dose administered over a 21-day cycle Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) administered over a 21-day cycle
Drug: CC-92480
CC-92480

Drug: Bortezomib
Bortezomib

Drug: Dexamethasone
Dexamethasone
Experimental: CC-92480 in combination with carfilzomib and dexamethasone
Subjects in cohort C and F will receive following: Oral CC-92480 at specified cohort dose administered over a 28-day cycle Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects >75 years old) administered over a 28-day cycle
Drug: CC-92480
CC-92480

Drug: Dexamethasone
Dexamethasone

Drug: Carfilzomib
Carfilzomib
Experimental: CC-92480 in combination with daratumumab and dexamethasone
Subjects in cohorts B and E will receive following: Oral CC-92480 at specified cohort dose administered over a 28-day cycle Intravenous (IV) daratumumab 16 mg/kg administered over a 28-day cycle Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle
Drug: CC-92480
CC-92480

Drug: Dexamethasone
Dexamethasone

Drug: Daratumumab
Daratumumab
outcome measures
Primary Outcome Measures: 1. 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 .
2. 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
3. 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
Secondary Outcome Measures: 1. 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
2. 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
3. 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)
4. 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

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

Inclusion Criteria:

1. Subjects is ≥ 18 years of age and has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

2. Relapsed or refractory subjects must have measurable disease and have documented disease progression during or after their last anti-myeloma regimen.

3. Newly diagnosed subjects must have documented diagnosis with previously untreated symptomatic multiple myeloma.

4. Females of childbearing potential (FCBP) and male subjects must agree with the pregnancy prevention plan.

Exclusion Criteria:

1. Subject has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

2. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis.


Contacts and Locations
Contacts

Contact:

Locations
United States, Colorado Colorado Blood Cancer Institute Denver
United States, Florida H. Lee Moffitt Cancer Center and Research Institute Tampa
United States, Georgia Winship Cancer Institute of Emory University Atlanta
United States, Illinois Northwestern University Feinberg School of Medicine Chicago
United States, Illinois University of Chicago Medicine Chicago
United States, Massachusetts Massachusetts General Hospital Boston
United States, Massachusetts Dana-Farber Cancer Institute Boston
United States, Massachusetts Beth Israel Deaconess Medical Center Boston
United States, Michigan Barbara Ann Karmanos Cancer Center Detroit
United States, Minnesota Mayo Clinic Rochester
United States, New Jersey Hackensack University Medical Center Hackensack
United States, North Carolina Wake Forest University Baptist Medical Center Winston-Salem
United States, Ohio The Ohio State University Comprehensive Cancer Center Columbus
United States, Tennessee Sarah Cannon Cancer Center Nashville
United States, Texas The University of Texas - MD Anderson Cancer Center Houston
United States, Washington Swedish Cancer Institute Seattle
Canada, Alberta Tom Baker Cancer Center Calgary
Canada, Alberta University of Alberta - Faculty of Medicine and Dentistry Edmonton
Canada, Nova Scotia Queen Elizabeth II Health Sciences Centre Halifax
Canada, Ontario Princess Margaret Cancer Centre Toronto
Canada, Quebec Hopital Maisonneuve Rosemont dba CIUSSS de lEst de lIle de Montreal Montreal
Czechia Fakultni Nemocnice Brno Brno
Czechia Fakultni Nemocnice Ostrava Ostrava-Poruba
Czechia Charles University General Hospital Praha 2
Denmark Rigshospitalet University Hospital Copenhagen
Denmark Odense University Hospital Odense
Denmark Vejle Hospital Vejle
France Hopital Claude Huriez CHRU Lille Lille cedex
France Institut Paoli Calmette Hematologie Marseille cedex
France Hotel Dieu CHU Nantes Nantes Cedex 01
France Institut Universitaire du Cancer de Toulouse (IUCT) - Oncopole Toulouse Cedex 9
France CHRU Hopital Bretonneau Tours cedex
Germany Universitatsklinikum Freiburg Medizinische Klinik und Poliklinik Freiburg
Germany Universitaetsklinikum Hamburg-Eppendorf Hamburg
Germany Universitaetsklinikum Heidelberg Heidelberg
Germany Klinikum rechts der Isar der Technischen Universitaet Muenchen Munchen
Germany Universitaets-klinikum Wuerzburg Wuerzburg
Greece Alexandra General Hospital of Athens Athens
Italy ASST Spedali Civili P.O. di Brescia Brescia
Italy Fondazione IRCCS Istituto Nazionale dei Tumori Milan
Italy Azienda Ospedaliera di Reggio Emilia - Arcispedale Santa Maria Nuova Reggio Emilia
Italy Azienda Ospedaliera Citta della Salute e della Scienza di Torino Torino
Spain Hopsital Germans Trias I Pujol Badalona
Spain Hospital Universitario 12 de Octubre Madrid
Spain Clinica Universidad de Navarra Pamplona
Spain Universitario de Salamanca - Hospital Clinico Salamanca
Spain Hospital Universtario Marques de Valdecilla Santander
Sponsors and Collaborators
Celgene
Investigator
Study Director : Tsvetan Biyukov, MD Bristol-Myers Squibb
More Information
Responsible Party : Celgene
ClinicalTrials.gov Identifier : NCT03989414     
Other Study ID Numbers : CC-92480-MM-002, U1111-1233-5619, 2018-004767-31
First Posted : June 18, 2019
Last Update Posted : October 2, 2020
Last Verified : September 2020
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.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene: CC-92480
Relapsed or Refractory Multiple Myeloma
Newly Diagnosed Multiple Myeloma
Multiple Myeloma
Additional relevant MeSH terms :
Multiple Myeloma
Neoplasms, Plasma Cell