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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03275285




Registration number
NCT03275285
Ethics application status
Date submitted
5/09/2017
Date registered
7/09/2017

Titles & IDs
Public title
Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients
Scientific title
Randomized, Open Label, Multicenter Study Assessing The Clinical Benefit Of Isatuximab Combined With Carfilzomib (Kyprolis®) And Dexamethasone Versus Carfilzomib With Dexamethasone In Patients With Relapse And/Or Refractory Multiple Myeloma Previously Treated With 1 to 3 Prior Lines
Secondary ID [1] 0 0
U1111-1195-5957
Secondary ID [2] 0 0
EFC15246
Universal Trial Number (UTN)
Trial acronym
IKEMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plasma Cell 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 - isatuximab SAR650984
Treatment: Drugs - carfilzomib
Treatment: Drugs - dexamethasone

Experimental: Isatuximab + Carfilzomib + Dexamethasone (IKd) - Isatuximab (intravenous) on day 1, 8, 15 and 22 of 1st cycle, then on day 1 and 15 of subsequent cycles in combination with carfilzomib (intravenous) on day 1, 2, 8, 9, 15 and 16 + dexamethasone (intravenous or by mouth \[po\]) on day 1, 2, 8, 9, 15, 16, 22 and 23 of a 28 day cycle.

Active comparator: Carfilzomib + Dexamethasone (Kd) - Carfilzomib (intravenous) on day 1, 2, 8, 9, 15, 16 + dexamethasone (intravenous or po) on day 1, 2, 8, 9, 15, 16, 22 and 23 of a 28 day cycle.


Treatment: Drugs: isatuximab SAR650984
Pharmaceutical form: solution for infusion

Route of administration: intravenous

Treatment: Drugs: carfilzomib
Pharmaceutical form: solution for infusion

Route of administration: intravenous

Treatment: Drugs: dexamethasone
Pharmaceutical form: tablets or solution for infusion

Route of administration: oral or intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis
Timepoint [1] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months)
Primary outcome [2] 0 0
Progression Free Survival as Determined by Independent Response Committee: [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Primary Analysis
Timepoint [2] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Primary outcome [3] 0 0
Progression Free Survival as Determined by Independent Response Committee: Final Analysis
Timepoint [3] 0 0
From randomization until the final analysis data cut-off date of 14 January 2022 (the median duration of follow-up was 43.96 months)
Primary outcome [4] 0 0
Progression Free Survival as Determined by Independent Response Committee [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Final Analysis
Timepoint [4] 0 0
From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
Secondary outcome [1] 0 0
Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis
Timepoint [1] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [2] 0 0
Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis
Timepoint [2] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [3] 0 0
Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis
Timepoint [3] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [4] 0 0
Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Final Analysis
Timepoint [4] 0 0
From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
Secondary outcome [5] 0 0
Percentage of Participants With Complete Response (CR) as Per Independent Response Committee: Final Analysis
Timepoint [5] 0 0
From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
Secondary outcome [6] 0 0
Percentage of Participants With Complete Response With MRD Negativity: Final Analysis
Timepoint [6] 0 0
From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
Secondary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
From randomization until the final analysis data cut-off date of 7 Feb 2023 (the median duration of follow-up was 56.61 months)
Secondary outcome [8] 0 0
Duration of Response (DOR): Primary Analysis
Timepoint [8] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [9] 0 0
Time to Progression (TTP): Primary Analysis
Timepoint [9] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [10] 0 0
Time to First Response: Primary Analysis
Timepoint [10] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [11] 0 0
Time to Best Response: Primary Analysis
Timepoint [11] 0 0
From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
Secondary outcome [12] 0 0
Second Progression Free Survival (PFS2): Final Analysis - Data Cut-off Date of 14 Jan 2022
Timepoint [12] 0 0
From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
Secondary outcome [13] 0 0
Second Progression Free Survival (PFS2): Overal Survival Analysis - Data Cut-off Date of 07 Feb 2023
Timepoint [13] 0 0
From randomization until the overal survival analysis data cut-off date of 07 Feb 2023 (the median duration of follow-up was 56.61 months)
Secondary outcome [14] 0 0
Number of Participants With Renal Response (RR): Primary Analysis
Timepoint [14] 0 0
From the first dose of study treatment to 30 days following the last administration of study treatment (maximum duration: up to 114 weeks)
Secondary outcome [15] 0 0
Health Related Quality of Life (HRQL): Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status Score at Specified Timepoints
Timepoint [15] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [16] 0 0
HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score at Specified Timepoints: Primary Analysis
Timepoint [16] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [17] 0 0
HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment at Specified Timepoints: Primary Analysis
Timepoint [17] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [18] 0 0
HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Body Image Score at Specified Timepoints: Primary Analysis
Timepoint [18] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [19] 0 0
HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Future Perspective at Specified Timepoints: Primary Analysis
Timepoint [19] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [20] 0 0
HRQL: Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints: Primary Analysis
Timepoint [20] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [21] 0 0
HRQL: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints: Primary Analysis
Timepoint [21] 0 0
Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
Secondary outcome [22] 0 0
Pharmacokinetics: Plasma Concentration at End of Infusion (Ceoi) of Isatuximab: Primary Analysis
Timepoint [22] 0 0
End of infusion on Cycle 1 Day 1 and Cycle 1 Day 15; Cycle 2 Day 1
Secondary outcome [23] 0 0
Pharmacokinetics: Plasma Concentration of Isatuximab at Ctrough: Primary Analysis
Timepoint [23] 0 0
Pre-infusion on Cycle 1 Day 1, Day 8, Day 15 and Day 22, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 and Cycle 10 Day 1
Secondary outcome [24] 0 0
Pharmacokinetics: Maximum Observed Concentration (Cmax) of Carfilzomib: Primary Analysis
Timepoint [24] 0 0
Cycle 1: pre-dose (0 hour), 30 minutes (min), 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [25] 0 0
Pharmacokinetics: Clast of Carfilzomib: Primary Analysis
Timepoint [25] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [26] 0 0
Pharmacokinetics: Tmax of Carfilzomib: Primary Analysis
Timepoint [26] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [27] 0 0
Pharmacokinetics: Tlast of Carfilzomib: Primary Analysis
Timepoint [27] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [28] 0 0
Pharmacokinetics: Area Under the Plasma Concentration Time Curve (AUC) of Carfilzomib: Primary Analysis
Timepoint [28] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [29] 0 0
Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) of Carfilzomib: Primary Analysis
Timepoint [29] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [30] 0 0
Pharmacokinetics: Percentage of Extrapolation of AUC (AUCext) of Carfilzomib: Primary Analysis
Timepoint [30] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [31] 0 0
Pharmacokinetics: Terminal Half-life (t1/2z) of Carfilzomib: Primary Analysis
Timepoint [31] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [32] 0 0
Pharmacokinetics: Clearance at Steady State (CLss) of Carfilzomib: Primary Analysis
Timepoint [32] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [33] 0 0
Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Carfilzomib: Primary Analysis
Timepoint [33] 0 0
Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
Secondary outcome [34] 0 0
Number of Participants With Anti-Drug Antibodies (ADA): Primary Analysis
Timepoint [34] 0 0
From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: 111 weeks)
Secondary outcome [35] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs): Final Analysis
Timepoint [35] 0 0
From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 265 weeks for Kd arm and 268 weeks for IKd arm)

Eligibility
Key inclusion criteria
Inclusion criteria:

* Participants with MM previously treated with prior 1 to 3 lines and with measurable serum M-protein (>= 0.5 gram/deciliter) and/or urine M-protein (>= 200 milligram/24 hours).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Participants previously pretreated with carfilzomib, who never achieved at least one minor response during previous therapies and/or last previous therapy completed within 14 last days.
* Participants with serum free light chain (FLC) measurable disease only.
* Participants less than 18 years old, participants with Eastern Cooperative Oncology Group performance status more than 2.
* Participants with inadequate biological tests.
* Participants with myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure, superior or equal to grade 3 arrhythmias, stroke or transient ischemic attack within last 6 months, and/or left ventricular ejection fraction lower than 40%.
* Participants with previous cancer unless disease free for more than 5 years or in situ cancer curatively treated.
* Participants with known acquired immunodeficiency syndrome related illness or human immunodeficiency virus requiring antiretroviral treatment, or hepatitis A, B, or C active infection.
* Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
25/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/11/2024
Actual
Sample size
Target
Accrual to date
Final
302
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Investigational Site Number : 0360005 - Blacktown
Recruitment hospital [2] 0 0
Investigational Site Number : 0360006 - Tweed Heads
Recruitment hospital [3] 0 0
Investigational Site Number : 0360002 - Wollongong
Recruitment hospital [4] 0 0
Investigational Site Number : 0360001 - Fitzroy
Recruitment hospital [5] 0 0
Investigational Site Number : 0360004 - Heidelberg West
Recruitment hospital [6] 0 0
Investigational Site Number : 0360007 - Nedlands
Recruitment hospital [7] 0 0
Investigational Site Number : 0360008 - West Perth
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
South Carolina
Country [3] 0 0
Brazil
State/province [3] 0 0
Bahia
Country [4] 0 0
Brazil
State/province [4] 0 0
Rio Grande Do Sul
Country [5] 0 0
Brazil
State/province [5] 0 0
São Paulo
Country [6] 0 0
Brazil
State/province [6] 0 0
Rio De Janeiro
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Canada
State/province [8] 0 0
New Brunswick
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Czechia
State/province [10] 0 0
Brno
Country [11] 0 0
Czechia
State/province [11] 0 0
Olomouc
Country [12] 0 0
Czechia
State/province [12] 0 0
Ostrava - Poruba
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 2
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Nantes
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Pessac
Country [18] 0 0
France
State/province [18] 0 0
Pierre Benite
Country [19] 0 0
France
State/province [19] 0 0
POITIERS Cedex
Country [20] 0 0
Greece
State/province [20] 0 0
Athens
Country [21] 0 0
Greece
State/province [21] 0 0
Patra
Country [22] 0 0
Greece
State/province [22] 0 0
Thessaloniki
Country [23] 0 0
Hungary
State/province [23] 0 0
Budapest
Country [24] 0 0
Hungary
State/province [24] 0 0
Kaposvár
Country [25] 0 0
Italy
State/province [25] 0 0
Bologna
Country [26] 0 0
Italy
State/province [26] 0 0
Pisa
Country [27] 0 0
Italy
State/province [27] 0 0
Reggio Emilia
Country [28] 0 0
Italy
State/province [28] 0 0
Torino
Country [29] 0 0
Japan
State/province [29] 0 0
Iwate
Country [30] 0 0
Japan
State/province [30] 0 0
Kumamoto
Country [31] 0 0
Japan
State/province [31] 0 0
Nagano
Country [32] 0 0
Japan
State/province [32] 0 0
Shizuoka
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo
Country [34] 0 0
Japan
State/province [34] 0 0
Yamagata-shi
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul-teukbyeolsi
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Busan
Country [37] 0 0
New Zealand
State/province [37] 0 0
Auckland
Country [38] 0 0
New Zealand
State/province [38] 0 0
Wellington
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Ekaterinburg
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Kirov
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Novosibirsk
Country [42] 0 0
Spain
State/province [42] 0 0
Catalunya [Cataluña]
Country [43] 0 0
Spain
State/province [43] 0 0
Valenciana, Comunidad
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Sevilla
Country [46] 0 0
Turkey
State/province [46] 0 0
Adana
Country [47] 0 0
Turkey
State/province [47] 0 0
Ankara
Country [48] 0 0
Turkey
State/province [48] 0 0
Bursa
Country [49] 0 0
Turkey
State/province [49] 0 0
Istanbul
Country [50] 0 0
Turkey
State/province [50] 0 0
Samsun
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Devon
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Leicestershire
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Somerset

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents



Results are available at https://clinicaltrials.gov/study/NCT03275285