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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02773030




Registration number
NCT02773030
Ethics application status
Date submitted
12/05/2016
Date registered
16/05/2016
Date last updated
22/04/2024

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/Phase 2
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
532
Accrual to date
Final
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
Amsterdam
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
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 monotherapy and CC-220 in combination with DEX for Relapsed Refractory Multiple
Myeloma (RRMM), CC-220 in combination with DEX and BTZ, and CC-220 in combination with DEX
and DARA for Newly Diagnosed Multiple Myeloma (NDMM).
Trial website
https://clinicaltrials.gov/ct2/show/NCT02773030
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