Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02773030




Registration number
NCT02773030
Ethics application status
Date submitted
12/05/2016
Date registered
16/05/2016
Date last updated
25/06/2024

Titles & IDs
Public title
A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma
Scientific title
A 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
Secondary ID [1] 0 0
U1111-1182-9200
Secondary ID [2] 0 0
CC-220-MM-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CC-220
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Daratumumab
Treatment: Drugs - Bortezomib
Treatment: Drugs - Carfilzomib

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

Experimental: Cohort B: CC-220 in combination with Dexamethasone (DEX) - 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.

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

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

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 a dose of 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.

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, and 8 at cycle =9 of each 21-day cycle.

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, and 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

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 C1D2; 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, and 23 of each 28-day cycle. The DEX dose will be 20 mg.

Experimental: Cohort I: CC-220 in combination with DEX in post BCMA RRMM - 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, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.

Experimental: Cohort J1: CC-220 in combination with DEX and BTZ in NDMM - Part 2 - Oral CC-220 at 1.0mg, 1.3mg or 1.6mg administered at cycles 1 to 8 on Days 1 to 14 of each 21-day cycle and cycles = 9 on Days 1 to 21 of each 28-day cycle.

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.

Experimental: Cohort J2: 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.

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.

Experimental: Cohort C: CC-220 Monotherapy in RRMM - Part 2 - CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.


Treatment: Drugs: CC-220
Specified dose on specified days

Treatment: Drugs: Dexamethasone
Specified dose on specified days

Treatment: Drugs: Daratumumab
Specified dose on specified days

Treatment: Drugs: Bortezomib
Specified dose on specified days

Treatment: Drugs: Carfilzomib
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment
Timepoint [1] 0 0
Approximately 3 years
Primary outcome [2] 0 0
Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment
Timepoint [2] 0 0
Approximately 3 years
Primary outcome [3] 0 0
Overall response rate (ORR) of CC-220 in combination with Dexamethasone (DEX) in Cohort D
Timepoint [3] 0 0
Approximately 5 years
Secondary outcome [1] 0 0
Adverse Events (AEs)
Timepoint [1] 0 0
Approximately 5 years
Secondary outcome [2] 0 0
Overall response rate (ORR)
Timepoint [2] 0 0
Approximately 5 years
Secondary outcome [3] 0 0
Time to Response (TTR)
Timepoint [3] 0 0
Approximately 5 years
Secondary outcome [4] 0 0
Duration of Response (DOR)
Timepoint [4] 0 0
Approximately 5 years
Secondary outcome [5] 0 0
Progression-free Survival (PFS)
Timepoint [5] 0 0
Approximately 5 years
Secondary outcome [6] 0 0
Overall Survival (OS) in Part 2 relapsed and refractory multiple myeloma (RRMM) cohorts
Timepoint [6] 0 0
Approximately 5 years
Secondary outcome [7] 0 0
Pharmacokinetics - Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC[TAU])
Timepoint [7] 0 0
Approximately 1 year
Secondary outcome [8] 0 0
Pharmacokinetics - Maximum plasma concentration of drug (Cmax)
Timepoint [8] 0 0
Approximately 1 year
Secondary outcome [9] 0 0
Pharmacokinetics - Time to maximum plasma concentration of drug (Tmax)
Timepoint [9] 0 0
Approximately 1 year
Secondary outcome [10] 0 0
Very good partial response or better rate (VGPR)
Timepoint [10] 0 0
Approximately 4 years

Eligibility
Key inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
* Relapsed and refractory multiple myeloma (RRMM) participants must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
* Newly diagnosed multiple myeloma (NDMM) participants must have documented diagnosis with previously untreated symptomatic multiple myeloma (MM)
* Participants in Cohorts J1 and K are those for whom autologous stem cell transplantation is not planned for initial therapy or are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study
* Nonsecretory multiple myeloma
* Prior history of malignancies, other than MM and select non-invasive malignancies, unless the participant has been free of the disease for = 5 years

Other protocol-defined inclusion/exclusion criteria apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/02/2028
Actual
Sample size
Target
Accrual to date
Final
466
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 854 - Adelaide
Recruitment hospital [2] 0 0
Local Institution - 852 - Box Hill
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Nova Scotia
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
France
State/province [24] 0 0
Lile Cedax
Country [25] 0 0
France
State/province [25] 0 0
Pessac
Country [26] 0 0
France
State/province [26] 0 0
Pierre Benite cedex
Country [27] 0 0
France
State/province [27] 0 0
Poitiers Cedex
Country [28] 0 0
Germany
State/province [28] 0 0
Dresden
Country [29] 0 0
Germany
State/province [29] 0 0
Dusseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Heidelberg
Country [32] 0 0
Germany
State/province [32] 0 0
Tuebingen
Country [33] 0 0
Germany
State/province [33] 0 0
Wuerzburg
Country [34] 0 0
Israel
State/province [34] 0 0
Yerushalayim
Country [35] 0 0
Israel
State/province [35] 0 0
Tel Hashomer
Country [36] 0 0
Israel
State/province [36] 0 0
Tel-Aviv
Country [37] 0 0
Italy
State/province [37] 0 0
Meldola
Country [38] 0 0
Italy
State/province [38] 0 0
Pavia
Country [39] 0 0
Italy
State/province [39] 0 0
Reggio Emilia
Country [40] 0 0
Italy
State/province [40] 0 0
Rome
Country [41] 0 0
Italy
State/province [41] 0 0
Torino
Country [42] 0 0
Japan
State/province [42] 0 0
Ehime
Country [43] 0 0
Japan
State/province [43] 0 0
Aomori
Country [44] 0 0
Japan
State/province [44] 0 0
Hiroshima City
Country [45] 0 0
Japan
State/province [45] 0 0
Isehara City, Kanagawa
Country [46] 0 0
Japan
State/province [46] 0 0
Kamogawa
Country [47] 0 0
Japan
State/province [47] 0 0
Kyoto-city
Country [48] 0 0
Japan
State/province [48] 0 0
Nagasaki-shi
Country [49] 0 0
Japan
State/province [49] 0 0
Nagoya
Country [50] 0 0
Japan
State/province [50] 0 0
Ogaki
Country [51] 0 0
Japan
State/province [51] 0 0
Osaka
Country [52] 0 0
Japan
State/province [52] 0 0
Sendai
Country [53] 0 0
Japan
State/province [53] 0 0
Shinagawa-ku, Tokyo
Country [54] 0 0
Japan
State/province [54] 0 0
Sunto-gun
Country [55] 0 0
Japan
State/province [55] 0 0
Toyohashi
Country [56] 0 0
Netherlands
State/province [56] 0 0
NH
Country [57] 0 0
Netherlands
State/province [57] 0 0
Maastrich
Country [58] 0 0
Netherlands
State/province [58] 0 0
Rotterdam
Country [59] 0 0
Netherlands
State/province [59] 0 0
Utrecht
Country [60] 0 0
Spain
State/province [60] 0 0
Badalona (Barcelona)
Country [61] 0 0
Spain
State/province [61] 0 0
Barcelona
Country [62] 0 0
Spain
State/province [62] 0 0
Madrid
Country [63] 0 0
Spain
State/province [63] 0 0
Pamplona
Country [64] 0 0
Spain
State/province [64] 0 0
Valencia
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Birmingham
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Leeds
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Oxford
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02773030