Trial Review

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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
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Ohio
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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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
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France
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Lile Cedax
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France
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Pessac
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France
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Pierre Benite cedex
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France
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Poitiers Cedex
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Germany
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Dresden
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Germany
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Dusseldorf
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Tuebingen
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Germany
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Wuerzburg
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Israel
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Yerushalayim
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Israel
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Tel Hashomer
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Israel
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Tel-Aviv
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Italy
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Meldola
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Italy
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Pavia
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Italy
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Reggio Emilia
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Italy
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Rome
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Italy
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Torino
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Japan
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Ehime
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Japan
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Aomori
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Japan
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Hiroshima City
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Japan
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Isehara City, Kanagawa
Country [46] 0 0
Japan
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Kamogawa
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Japan
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Kyoto-city
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Japan
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Nagasaki-shi
Country [49] 0 0
Japan
State/province [49] 0 0
Nagoya
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Japan
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Ogaki
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Japan
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Osaka
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Japan
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Sendai
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Japan
State/province [53] 0 0
Shinagawa-ku, Tokyo
Country [54] 0 0
Japan
State/province [54] 0 0
Sunto-gun
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Japan
State/province [55] 0 0
Toyohashi
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Netherlands
State/province [56] 0 0
NH
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Netherlands
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Maastrich
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Netherlands
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Rotterdam
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Netherlands
State/province [59] 0 0
Utrecht
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Spain
State/province [60] 0 0
Badalona (Barcelona)
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
State/province [64] 0 0
Valencia
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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