A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple Myeloma

Phase 1b/2a Multicenter, Open-label, Dose-escalation Study to Determine the Maximum Tolerated Dose, Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CC-220 As Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma

This is a multicenter, multi-country, open-label, Phase 1b/2a dose-escalation study consisting of two parts: dose escalation (Part 1) for CC-220 monotherapy, CC-220 in combination with DEX, CC-220 in combination with DEX and DARA, CC-220 in combination with DEX and BTZ and CC-220 in combination with DEX and CFZ; and the expansion of the RP2D (Part 2) for CC-220 in combination with DEX for Relapsed Refractory Multiple Myeloma and CC-220 in combination with DEX and BTZ for Newly Diagnosed Multiple Myeloma.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib; Drug: Daratumumab; Drug: CC-220; Drug: Dexamethasone; Drug: Daratumumab - 16mg/kg; Drug: Daratumumab- 1800mg; Drug: Bortezomib (BTZ); Drug: Carfilzomib

Detailed Description

Subjects assigned to CC-220 monotherapy, who develop progressive disease (PD) will have the option to receive DEX in addition to CC-220 after consultation with the Medical Monitor. The dose of CC-220 will not be higher than the dose of CC-220 used in combination with dexamethasone in Cohort B that has been determined to be safe. Progressive disease must be confirmed in accordance with international myeloma working group (IMWG) criteria.

The starting dose of DEX will be 40 mg for subjects who are ≤75 years of age and 20 mg for subjects who are >75 years of age, given once weekly. This treatment will continue until PD, unacceptable toxicity or the subject withdraws consent.

For Cohorts A and B, the starting dose level of CC-220, dose level 1, is 0.3 mg. A dose level -1, of 0.15 mg, may also be evaluated if the starting dose level of 0.3 mg for 21 days of a 28-day cycle is not tolerated. For Cohorts E and F, the starting dose level of CC-220, dose level 1, is one dose level below the maximum dose for Cohort B that has been determined to be safe by the dose escalation committee (DEC) at the start of enrollment for both cohorts. For Cohort E in addition to CC-220 and DEX, daratumumab will be administered intravenously (IV) at a 16mg/kg dose. For Cohort F in addition to CC-220 and DEX, bortezomib will be administered subcutaneous (SC) at a 1.3mg/m2 dose.

All subjects with a minimal response (MR) or better who discontinue study treatment in Part 1 or Part 2 of the study for a reason other than PD or withdrawal of consent from the study will be followed for response assessment every 28 days (every 21 days for Cohort F) until PD.

The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

The initiation of Part 2 will begin when the RP2D is established in Part 1 in either Cohort A or Cohort B. Either cohort may begin once the RP2D is determined for each cohort independently during Part 1. All expansion decisions will be determined by the DEC after review of all safety, PK, biomarker and preliminary efficacy data, as applicable. During Part 2, the Independent Expert Reviewer will review safety data and any other data deemed relevant so that subject safety is ensured.

• Study Type: Interventional
• Enrollment (Actual): 466
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution - 854
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Local Institution - 852
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 904
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Local Institution - 901
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth II Health Sciences Centre
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Local Institution - 902
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center - Royal Victoria Hospital
    • Montreal, Quebec, Canada, H4A 3J1
      • Local Institution - 903
• France
  • Lile Cedax, France, 59037
    • CHRU Hôpital Claude Huriez
  • Lile Cedax, France, 59037
    • Local Institution - 704
  • Pessac, France, 33604
    • CHU Bordeaux
  • Pessac, France, 33604
    • Local Institution - 701
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Pierre-Bénite, France, 69495
    • Local Institution - 703
  • Poitiers, France, 86021
    • Chu La Miletrie
  • Poitiers, France, 86021
    • Local Institution - 702
• Germany
  • Dresden, Germany, 01307
    • Medizinische Kinik und Poliklinik I
  • Dresden, Germany, 01307
    • Local Institution - 605
  • Düsseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Düsseldorf, Germany, 40225
    • Local Institution - 603
  • Hamburg, Germany, 20246
    • Universitaetsklinik Hamburg - Eppendorf
  • Hamburg, Germany, 20246
    • Local Institution - 604
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Heidelberg, Germany, 69120
    • Local Institution - 602
  • Tübingen, Germany, 72076
    • Local Institution - 601
  • Tübingen, Germany, 72076
    • UKT Universitaetsklinikum Tuebingen
  • Würzburg, Germany, 97080
    • Local Institution - 606
  • Würzburg, Germany, 97080
    • Universitaets-klinikum Wuerzburg
• Israel
  • Tel Aviv, Israel, 64239
    • Local Institution - 755
  • Tel Litwinsky, Israel, 52620
    • Local Institution - 754
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91031
      • Local Institution - 751
• Italy
  • Meldola, Italy, 47014
    • Local Institution - 307
  • Pavia, Italy, 27100
    • I.R.C.C.S. Policlinico San Matteo - Universita di Pavia
  • Pavia, Italy, 27100
    • Local Institution - 305
  • Reggio Emilia, Italy, 42100
    • Azienda Ospedaliera di Reggio Emilia - Arcispedale Santa Maria Nuova
  • Reggio Emilia, Italy, 42100
    • Local Institution - 302
  • Rome, Italy, 00161
    • Local Institution - 303
  • Rome, Italy, 00161
    • Universita degli Studi di Roma La Sapienza - Umberto I Policlinico di Roma - Centro di Ematologia
  • Torino, Italy, 10126
    • Osp. S.Giovanni Battista Le Molinette
  • Torino, Italy, 10126
    • Local Institution - 301
• Japan
  • Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Aomori, Japan, 030-8553
    • Local Institution - 805
  • Hiroshima, Japan, 730-8619
    • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
  • Hiroshima, Japan, 730-8619
    • Local Institution - 813
  • Isehara City, Kanagawa, Japan, 259-1193
    • Tokai University Hospital
  • Isehara City, Kanagawa, Japan, 259-1193
    • Local Institution - 812
  • Kamogawa, Japan, 296-8602
    • Kameda Medical Center
  • Kamogawa, Japan, 296-8602
    • Local Institution - 809
  • Kyoto, Japan, 602-8566
    • University Hospital, Kyoto Prefectural University of Medicine
  • Kyoto, Japan, 602-8566
    • Local Institution - 802
  • Matsuyama, Japan, 790-8524
    • Matsuyama Red Cross Hospital
  • Nagasaki, Japan, 8528511
    • Japanese Red Cross Nagasaki Genbaku Hospital
  • Nagasaki, Japan, 8528511
    • Local Institution - 811
  • Nagoya, Japan, 467-8602
    • Nagoya City University Hospital
  • Nagoya, Japan, 464-8681
    • Aichi Cancer Center
  • Nagoya, Japan, 464-8681
    • Local Institution - 810
  • Nagoya, Japan, 467-8602
    • Local Institution - 801
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Osaka, Japan, 545-8586
    • Local Institution - 804
  • Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Sendai, Japan, 980-8574
    • Local Institution - 803
  • Shinagawa-ku, Tokyo, Japan, 141-8625
    • NTT Medical Center Tokyo
  • Shinagawa-ku, Tokyo, Japan, 141-8625
    • Local Institution - 806
  • Sunto-gun, Japan, 411-8777
    • Shizuoka Cancer Center
  • Sunto-gun, Japan, 411-8777
    • Local Institution - 814
  • Toyohashi, Japan, 441-8570
    • Toyohashi Municipal Hospital
  • Toyohashi, Japan, 441-8570
    • Local Institution - 807
  • Ōgaki, Japan, 503-8502
    • Ogaki Municipal Hospital
  • Ōgaki, Japan, 503-8502
    • Local Institution - 815
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Local Institution - 808
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center
  • Maastrich, Netherlands, 6202 AZ
    • Maastricht University Medical Center
  • Maastrich, Netherlands, 6202 AZ
    • Local Institution - 504
  • Rotterdam, Netherlands, 3075 EA
    • Erasmus Medical Center
  • Rotterdam, Netherlands, 3075 EA
    • Local Institution - 501
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
  • Utrecht, Netherlands, 3584 CX
    • Local Institution - 502
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Local Institution - 503
• Spain
  • Badalona (Barcelona), Spain, 08916
    • Hospital Universitari Germans Trias i Pujol Can Ruti
  • Badalona (Barcelona), Spain, 08916
    • Local Institution - 404
  • Barcelona, Spain, 08035
    • Hospital Val d'Hebron
  • Barcelona, Spain, 08908
    • Instituto Catalan de Oncologia-Hospital Duran i Reynals
  • Barcelona, Spain, 08035
    • Local Institution - 401
  • Barcelona, Spain, 08908
    • Local Institution - 405
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañón
  • Madrid, Spain, 28007
    • Local Institution - 408
  • Madrid, Spain, 28034
    • Local Institution - 407
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Pamplona, Spain, 31008
    • Local Institution - 402
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Pesset
  • Valencia, Spain, 46017
    • Local Institution - 406
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
  • Birmingham, United Kingdom, B15 2TH
    • Local Institution - 205
  • Leeds, United Kingdom, LS9 7TF
    • Saint James University Hospital
  • Leeds, United Kingdom, LS9 7TF
    • Local Institution - 202
  • Oxford, United Kingdom, OX4 6LB
    • Local Institution - 204
  • Oxford, United Kingdom, OX4 6LB
    • Genesis Care
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5NG
    • Local Institution - 201
  • Sutton, United Kingdom, SM2 5PT
    • Local Institution - 203
  • Sutton, United Kingdom, SM2 5NG
    • The Institut of Cancer Research
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
    • Scottsdale, Arizona, United States, 85259
      • Local Institution - 102
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Local Institution - 107
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 101
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H Lurie Comprehensive Cancer Center NW Univ
    • Chicago, Illinois, United States, 60611
      • Local Institution - 120
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Cancer Center
    • Fairway, Kansas, United States, 66205
      • Local Institution - 113
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Med
    • Baltimore, Maryland, United States, 21201
      • Local Institution - 106
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02117
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber/Mass General Brigham Cancer Care, Inc
    • Boston, Massachusetts, United States, 02115
      • Local Institution - 114
    • Boston, Massachusetts, United States, 02117
      • Local Institution - 115
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 110
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 104
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201
      • Local Institution - 103
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Local Institution - 140
    • Grand Island, Nebraska, United States, 68803
      • Local Institution - 141
    • Omaha, Nebraska, United States, 68114
      • Local Institution - 137
    • Omaha, Nebraska, United States, 68124
      • Local Institution - 138
    • Omaha, Nebraska, United States, 68130
      • Local Institution - 131
    • Papillion, Nebraska, United States, 68046
      • Local Institution - 139
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • Local Institution - 756
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 108
  • New York
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
    • Mineola, New York, United States, 11501
      • Local Institution - 122
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai Medical Center
    • New York, New York, United States, 10016
      • Local Institution - 121
    • New York, New York, United States, 10029
      • Local Institution - 109
    • New York, New York, United States, 10065
      • Local Institution - 111
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital Weil Cornell Medical College
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center
    • Rochester, New York, United States, 14642
      • Local Institution - 125
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 112
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 117
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43210
      • Local Institution - 124
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 116
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute
    • Greenville, South Carolina, United States, 29605
      • Local Institution - 123
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Local Institution - 134
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75390
      • Local Institution - 118
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Local Institution - 119
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute at the University of Utah
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 126
    • Tacoma, Washington, United States, 98405
      • Local Institution - 132

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All subjects in RRMM cohorts must have a documented diagnosis of Multiple Myeloma and have measurable disease defined as:

1. M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP ≥0.5 g/dL or uPEP ≥200 mg/24 hours and/or

2. Light chain Multiple Myeloma without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio 2. All subjects in RRMM cohorts must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy. Subjects who had CAR T therapy as their last myeloma therapy must have documented disease progression.

   3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 3. Subject must have documented diagnosis with previously untreated symptomatic MM as defined by the criteria below (Rajkumar, 2016): MM diagnostic criteria;

   - Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma

   - Any one or more of the following myeloma defining events:

   • One or more of the following myeloma-related organ dysfunction (at least one of the following);

     • [C] Calcium elevation (serum calcium > 0.25 mmol/L [> 1 mg/dL] higher than the upper limit of laboratory normal or > 2.75 mmol/L [> 11 mg/dL])

     • [R] Renal insufficiency (serum creatinine > 2 mg/dl [> 177 μmol/L] or creatinine clearance < 40 ml/min)

     • [A] Anemia (hemoglobin < 10 g/dl or > 2 g/dL below the lower limit of laboratory normal)
     • [B] Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT

   • One or more of the following biomarkers of malignancy:

     • Clonal bone marrow plasma cell percentage* ≥ 60%
     • Abnormal serum free light-chain (FLC) ratio ≥ 100 (involved kappa) or <0.01 (involved lambda) and involved FLC level must be ≥ 100 mg/L
     • >1 focal lesion detected by magnetic resonance imaging (MRI) (at least 5 mm in size)

   AND have measurable disease, as assessed by central laboratory, defined by any of the following:

   - Immunoglobulin (Ig)G myeloma: serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours; or

   - IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or

   - Light chain multiple myeloma without measurable disease in serum or urine: serum FLC ≥ 100 mg/L and abnormal kappa lambda (κ/λ) ratio 4. Subjects in Cohort J1 are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation due to:

   - Age ≥65 years, OR

   - In subjects <65 years: presence of important comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with autologous stem cell transplantation.

   5. Subjects in Cohort J2 are considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory data.

   Exclusion Criteria:

   1. Subject has nonsecretory multiple myeloma 2. Subjects with Plasma Cell leukemia or amyloidosis 3. Any of the following laboratory abnormalities

   • Absolute neutrophil count (ANC) <1,000/μL

   • Platelet count < 75,000/μL for Part 1. For Part 2; platelet count < 75,000/μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count < 50,000/μL (transfusions are not permitted to achieve minimum platelet counts

   • Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)

   • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT)≥2.0 x upper limit of normal (ULN)
   • Serum total bilirubin and alkaline phosphatase >1.5 x ULN
   • Subjects with serious renal impairment creatinine clearance ([CrCl] <45 mL/min) or requiring dialysis would be excluded 4. Subjects with peripheral neuropathy ≥Grade 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: CC-220 Monotherapy - Part 1; Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle	Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide
Experimental: Cohort K: CC-220 with DEX and DARA in NDMM and not autologous stem cell transplant eligible - Part 2; Oral CC-220 at 1.0mg, 1.3mg or 1.6mg from Days 1-21 of each 28-day cycle. Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle. Subcutaneous DARA at 1800 mg over 3 to 5minutes on Days 1, 8, 15, and 22 at cycle 1-2 of a 28-day cycle, Days1, and 15 at cycle 3-6 of a 28-day cycle, and Day1 at cycle ≥7 of each 28-day cycle.	Drug: Daratumumab; Specified dose on specified days; Other Names: Darzalex
Experimental: Cohort B: CC-220 in combination with Dexamethasone - Part 1; Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, DEX will be administered at 20 mg on Days 1, 8,15, and 22 of each 28-day cycle. Subjects who surpass the age of 75 years while on treatment may be switched to the 20 mg QD dosage based on the investigator's best judgment.	Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron
Experimental: Cohort D: CC-220 in combination with Dexamethasone - Part 2; Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.	Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron
Experimental: Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1; Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Intravenous DARA at dose 16mg/kg on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle. Once the MTD and/or RP2D is determined in Cohort E (CC-220Dd), subjects will be enrolled at this dose level using SC DARA.; Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Subcutaneous DARA at dose 1800 mg over 3 to 5 minutes on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.	Drug: Daratumumab; Specified dose on specified days; Other Names: Darzalex; Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron; Drug: Daratumumab - 16mg/kg; Daratumumab (DARA) 16mg/kg by intravenous infusion on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.; Other Names: Darzalex; Drug: Daratumumab- 1800mg; Daratumumab (DARA) 1800 mg by subcutaneous injection on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.; Other Names: Darzalex Faspro
Experimental: Cohort F: CC-220 with DEX and bortezomib - Part 1; Oral CC-220 at dose specified by cohort dose level from Day 1-14 of each 21-day cycle.; Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, and 15 of each 21-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, and 15 of each 21-day cycle.; Subcutaneous BTZ at dose 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.	Drug: Bortezomib; Specified dose on specified days; Other Names: Velcade; Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron; Drug: Bortezomib (BTZ); Bortezomib 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.; Other Names: Velcade
Experimental: Cohort G1-CC-220 in combination with CFZ and DEX -Part 1; Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle; Intravenous (IV) CFZ (Carfilzomib)administered at a starting dose of 20 mg/m2 on C1D1; and at a dose specified by cohort dose level thereafter on days 1, 8, 15 of each 28-day cycle; Oral DEX (Dexamethasone) on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects ≤ 75 years old, the DEX dose will be 40 mg. For subjects > 75 years old, the DEX dose will be 20 mg	Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron; Drug: Carfilzomib; Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle.; Other Names: Kyprolis
Experimental: Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1; Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle; Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle; Oral DEX on Days 1, 2, 8, 9, 15, 16, 22, 23 of each 28-day cycle. The DEX dose will be 20 mg	Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron; Drug: Carfilzomib; Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle.; Other Names: Kyprolis
Experimental: CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2; Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.	Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron
Experimental: CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2; Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle (Cycle 1 to 8) and from Day 1-21 of each 28-day cycle (Cycle 9 and above).; Oral DEX at Cycles 1 to 8, 20 mg (≤ 75 years old) or 10 mg (> 75 years old) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle and Cycles ≥ 9, 40 mg (≤ 75 years old) or 20 mg (> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.; Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-8 of each 21-day cycle.	Drug: Bortezomib; Specified dose on specified days; Other Names: Velcade; Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron; Drug: Bortezomib (BTZ); Bortezomib 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.; Other Names: Velcade
Experimental: CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2; Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle.; Oral DEX at 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) for Cycles 1 to 6 on Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle.; Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-6 of each 21-day cycle.	Drug: Bortezomib; Specified dose on specified days; Other Names: Velcade; Drug: CC-220; CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.; Other Names: Iberdomide; Drug: Dexamethasone; Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.; Other Names: Decadron; Drug: Bortezomib (BTZ); Bortezomib 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.; Other Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities in Part 1.	The dose-limiting toxicity (DLT) population includes subjects who missed no more than 4 doses of CC-220, 2 doses of DEX, 1 dose of IV DARA (Cohort E), 1 dose of BTZ (Cohort F), or 1 dose of CFZ (Cohort G1 or G2) during Cycle 1 for reasons other than DLT. This population will be used for analyzing the primary endpoint regarding the determination of the MTD. Hematologic DLTs: Grade 4 neutropenia (ANC <500/μL for >5 days) Grade 3 neutropenia (ANC <1,000/μL) with fever ≥38.5°C Grade 4 thrombocytopenia (platelet count <25,000/μL) or Grade 3 thrombocytopenia with bleeding or need for platelet transfusion Any other grade 4 hematologic toxicity, except anemia, not resolving to pretreatment baseline within 72 hours. Non-hematologic DLT: Any non-hematological toxicity ≥ Grade 3, except alopecia and nausea controlled by medical management.	From first dose to 28 days post last dose (up to 28 days)
Overall Response Rate (ORR) in Cohort D and Cohort H2	Tumor response, including progressive disease (PD) according to the IMWG Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better.	Approximately on average (Cohort D: 21.14 weeks, Cohort H2: 22.11 Weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Related Adverse Events	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.	Approximately on average of (Cohort A: 16.23 Cohort B: 10.32 Cohort D: 18.68 Cohort E: 15.65 Cohort F: 12.66 Cohort G: 16.03 Cohort H1: 17.22 Cohort H2: 21.07 Cohort I: 17.10 Cohort J: 20.56 Cohort K: 13.56) Months
Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)	An adverse event of special interest (AESI) is one of scientific and medical interest specific to understanding the safety profile of the Investigational Product, CC-220, and may require close monitoring and rapid communication by the Investigator to the Sponsor. An AESI may be serious or nonserious. The rapid reporting of AESIs allows ongoing surveillance of these events in order to characterize and understand their association with the use of this investigational product.	Approximately on average of (Cohort A: 16.23 Cohort B: 10.32 Cohort D: 18.68 Cohort E: 15.65 Cohort F: 12.66 Cohort G: 16.03 Cohort H1: 17.22 Cohort H2: 21.07 Cohort I: 17.10 Cohort J: 20.56 Cohort K: 13.56) Months
Very Good Partial Response Rate (ORR) in Cohort J1 and Cohort K	The very good partial response or better (≥ VGPR) rate is defined as the proportion of subjects with best response of VGPR or better during the trial without administration of myeloma therapy other than study treatment. The ≥ VGPR rate with 95% confidence interval (CI) together with the proportions in each response category based on the IMWG Uniform Response Criteria.	On Average of (Cohort J: 86.21, Cohort K: 56.29) Weeks
Overall Response Rate (ORR)	Tumor response, including progressive disease (PD) according to the IMWG Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better.	On Average of (Cohort A: 44.96, Cohort B: 32.79, Cohort D: 21.14, Cohort E: 53.74, Cohort F: 46.34, Cohort G: 63.26, Cohort H1: 58.10, Cohort H2: 22.11, Cohort I: 20.96, Cohort J: 86.21, Cohort K: 56.29) Weeks
Time to Response (TTR)	Time to response is defined as the time from the first dose date of study treatment to the first date of documented response (PR or better). Time to response will be summarized for responders using descriptive statistics by cohort and dose level.	On Average of (Cohort A:19.14, Cohort B: 12.39, Cohort D: 7.54, Cohort E: 5.44, Cohort F: 4.97, Cohort G: 12.30, Cohort H: 4.14, Cohort I: 8.79, Cohort J: 4.76, Cohort K: 6.51) Weeks
Duration of Response	Duration of response is defined as time from the earliest date of documented response (PR or better) to the earliest date of disease progression per IMWG Uniform Response Criteria or death, whichever occurred first. Participants who do not have progression of disease or death will be censored on the last adequate response assessment date. Duration of response for responders will be summarized using Kaplan-Meier estimates by cohort and dose level as appropriate. Data will be collected and analyzed per Cohort Totals.	On Average of (Cohort A:161.33, Cohort B: 63.74, Cohort D: 39.16, Cohort E: 89.56, Cohort F: 69.24, Cohort G: 80.93, Cohort H1: 77.11, Cohort H2: 42.71, Cohort I: 36.80, Cohort J: 92.36, Cohort K: 51.85) Weeks
Progression Free Survival	Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first Data will be collected and analyzed per Cohort Totals.	On Average of (Cohort A: 44.96, Cohort B: 32.79, Cohort D: 21.14, Cohort E: 53.74, Cohort F: 46.34, Cohort G: 63.26, Cohort H1: 58.10, Cohort H2: 22.11, Cohort I: 20.96, Cohort J: 86.21, Cohort K: 56.29) Weeks
Overall Survival for Cohort D, Cohort H2 and Cohort I	Time from first dose of IP to death due to any cause Data will be collected and analyzed per Cohort Totals.	On Average of (Cohort D: 81.14 Cohort H2: 91.54 Cohort I: 74.20)Weeks
Auc(Tau)	Area under the plasma concentration time-curve. AUC over the dosing interval.	From Cycle 1 Day 1 to Cycle 1 Day 15 (15 days)
Cmax	Cmax is defined as maximum plasma concentration of the drug.	From Cycle 1 Day 1 to Cycle 1 Day 15 (15 days)
Tmax	Tmax is defined is the time to maximum plasma concentration.	From Cycle 1 Day 1 to Cycle 1 Day 15 (15 days)

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Lonial S, Popat R, Hulin C, Jagannath S, Oriol A, Richardson PG, Facon T, Weisel K, Larsen JT, Minnema MC, Abdallah AO, Badros AZ, Knop S, Stadtmauer EA, Cheng Y, Amatangelo M, Chen M, Nguyen TV, Amin A, Peluso T, van de Donk NWCJ. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022 Nov;9(11):e822-e832. doi: 10.1016/S2352-3026(22)00290-3. Epub 2022 Oct 6.
• Amatangelo M, Flynt E, Stong N, Ray P, Van Oekelen O, Wang M, Ortiz M, Maciag P, Peluso T, Parekh S, van de Donk NWCJ, Lonial S, Thakurta A. Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma. Cell Rep Med. 2024 Jun 18;5(6):101571. doi: 10.1016/j.xcrm.2024.101571. Epub 2024 May 21.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2016
• Primary Completion (Actual): May 9, 2024
• Study Completion (Estimated): July 28, 2028

Study Registration Dates

• First Submitted: May 12, 2016
• First Submitted That Met QC Criteria: May 12, 2016
• First Posted (Estimated): May 16, 2016

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Multiple Myeloma; Daratumumab; Efficacy; Pharmacokinetics; Relapsed; Refractory; Dexamethasone; CC-220; Bortezomib; Newly diagnosed multiple myeloma; Relapsed and refractory multiple myeloma; Newly diagnosed multiple myeloma transplant non-eligible
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Bortezomib; Dexamethasone; Calcium Dobesilate; carfilzomib; daratumumab; iberdomide
• Other Study ID Numbers: CC-220-MM-001; U1111-1182-9200 (Registry Identifier: WHO); 2016-000860-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No