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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03275285
Ethics application status
Date submitted
5/09/2017
Date registered
7/09/2017
Date last updated
22/07/2020

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
2017-001940-37
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) - The length of time between treatment allocation and a patient lives with the disease but it does not get worse
Timepoint [1] 0 0
Up to approximately 36 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) - The proportion of patients that have a response to their disease: stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR)
Timepoint [1] 0 0
Up to approximately 36 months
Secondary outcome [2] 0 0
Rate of VGPR or better - The proportion of patients with sCR, CR and VGPR
Timepoint [2] 0 0
Up to approximately 36 months
Secondary outcome [3] 0 0
CR rate - The proportion of patients with sCR and CR
Timepoint [3] 0 0
Up to approximately 36 months
Secondary outcome [4] 0 0
Rate of VGPR or better with MRD (Minimal Residual Disease) negativity - The proportion of patients for whom MRD assessed by sequencing is negative at any time after first dose of study treatment
Timepoint [4] 0 0
Up to approximately 36 months
Secondary outcome [5] 0 0
Overall Survival (OS) - The length of time from the treatment allocation for a disease that patients are still alive
Timepoint [5] 0 0
Up to approximately 72 months
Secondary outcome [6] 0 0
Time to Progression (TTP) - How long the study treatment last before disease progression occurs
Timepoint [6] 0 0
Up to approximately 36 months
Secondary outcome [7] 0 0
Second Progression Free Survival (PFS2) - The length of time between treatment allocation to the date of first documentation of PD after initiation of further anti-myeloma treatment or death from any cause, whichever happens first
Timepoint [7] 0 0
Up to approximately 36 months
Secondary outcome [8] 0 0
Duration of response (DOR) - How long from the first response is observed until disease progression
Timepoint [8] 0 0
Up to approximately 36 months
Secondary outcome [9] 0 0
Number of patients with adverse events according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grading scaling - To evaluate how many adverse events occur while taking study treatment
Timepoint [9] 0 0
Up to 30 days after last study treatment administration
Secondary outcome [10] 0 0
Patient-reported outcome measured with Quality of Life questionnaire - To evaluate change in daily activities from screening
Timepoint [10] 0 0
Screening to 90 days after last study treatment administration
Secondary outcome [11] 0 0
Pharmacokinetics of isatuximab - To evaluate the plasma concentration of isatuximab
Timepoint [11] 0 0
Up to approximately 10 months
Secondary outcome [12] 0 0
Pharmacokinetics of carfilzomib - To evaluate the plasma concentration of carfilzomib in 12 patients
Timepoint [12] 0 0
Up to 1 month
Secondary outcome [13] 0 0
Immunogenicity (ADA) - To evaluate presence of anti-drug antibodies against isatuximab
Timepoint [13] 0 0
Up to 13 months
Secondary outcome [14] 0 0
Time to first response - Length of time from treatment allocation to the date of first response (PR or better)
Timepoint [14] 0 0
Up to approximately 36 months
Secondary outcome [15] 0 0
Time to best response - Length of time from treatment allocation to the date of first best overall response (PR or better)
Timepoint [15] 0 0
Up to approximately 36 months

Eligibility
Key inclusion criteria
Inclusion criteria:

- Patients with multiple myeloma previously treated with prior 1 to 3 lines and with
measurable serum M-protein (= 0.5 g/dL) and/or urine M-protein (= 200 mg/24 hours).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Patients 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.

- Patients with serum free light chain (FLC) measurable disease only.

- Patients less than 18 years old, patients with Eastern Cooperative Oncology Group
performance status more than 2.

- Patients with inadequate biological tests.

- Patients 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%.

- Patients with previous cancer unless disease free for more than 5 years or in situ
cancer curatively treated.

- Patients with known acquired immunodeficiency syndrome related illness (AIDS) or human
immunodeficiency virus (HIV) requiring antiretroviral treatment, or hepatitis A, B, or
C active infection.

- Women of childbearing potential or male patient 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 patient'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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360005 - Blacktown
Recruitment hospital [2] 0 0
Investigational Site Number 0360001 - Fitzroy
Recruitment hospital [3] 0 0
Investigational Site Number 0360004 - Heidelberg West
Recruitment hospital [4] 0 0
Investigational Site Number 0360007 - Nedlands
Recruitment hospital [5] 0 0
Investigational Site Number 0360006 - Tweed Heads
Recruitment hospital [6] 0 0
Investigational Site Number 0360008 - West Perth
Recruitment hospital [7] 0 0
Investigational Site Number 0360002 - Wollongong
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [6] 0 0
6005 - West Perth
Recruitment postcode(s) [7] 0 0
2500 - Wollongong
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
Barretos
Country [4] 0 0
Brazil
State/province [4] 0 0
Porto Alegre
Country [5] 0 0
Brazil
State/province [5] 0 0
Rio De Janeiro
Country [6] 0 0
Brazil
State/province [6] 0 0
Salvador
Country [7] 0 0
Brazil
State/province [7] 0 0
Sao Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Montreal
Country [9] 0 0
Canada
State/province [9] 0 0
Saint John
Country [10] 0 0
Canada
State/province [10] 0 0
Surrey
Country [11] 0 0
Czechia
State/province [11] 0 0
Brno
Country [12] 0 0
Czechia
State/province [12] 0 0
Olomouc
Country [13] 0 0
Czechia
State/province [13] 0 0
Ostrava - Poruba
Country [14] 0 0
Czechia
State/province [14] 0 0
Praha 2
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Pessac
Country [19] 0 0
France
State/province [19] 0 0
Pierre Benite Cedex
Country [20] 0 0
France
State/province [20] 0 0
Poitiers Cedex
Country [21] 0 0
Greece
State/province [21] 0 0
Athens
Country [22] 0 0
Greece
State/province [22] 0 0
Patra
Country [23] 0 0
Greece
State/province [23] 0 0
Thessaloniki
Country [24] 0 0
Hungary
State/province [24] 0 0
Budapest
Country [25] 0 0
Hungary
State/province [25] 0 0
Kaposvár
Country [26] 0 0
Italy
State/province [26] 0 0
Bologna
Country [27] 0 0
Italy
State/province [27] 0 0
Pisa
Country [28] 0 0
Italy
State/province [28] 0 0
Reggio Emilia
Country [29] 0 0
Italy
State/province [29] 0 0
Torino
Country [30] 0 0
Japan
State/province [30] 0 0
Kumamoto-Shi
Country [31] 0 0
Japan
State/province [31] 0 0
Shibuya-Ku
Country [32] 0 0
Japan
State/province [32] 0 0
Shinjuku-Ku
Country [33] 0 0
Japan
State/province [33] 0 0
Shiwa-Gun
Country [34] 0 0
Japan
State/province [34] 0 0
Sunto-Gun
Country [35] 0 0
Japan
State/province [35] 0 0
Suwa-Shi
Country [36] 0 0
Japan
State/province [36] 0 0
Yamagata-Shi
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Busan
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Gangnam-Gu
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Seoul
Country [40] 0 0
New Zealand
State/province [40] 0 0
Auckland
Country [41] 0 0
New Zealand
State/province [41] 0 0
Wellington
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Ekaterinburg
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Kirov
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Novosibirsk
Country [45] 0 0
Spain
State/province [45] 0 0
Badalona
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Sevilla
Country [49] 0 0
Spain
State/province [49] 0 0
Valencia
Country [50] 0 0
Turkey
State/province [50] 0 0
Adana
Country [51] 0 0
Turkey
State/province [51] 0 0
Ankara
Country [52] 0 0
Turkey
State/province [52] 0 0
Bursa
Country [53] 0 0
Turkey
State/province [53] 0 0
Istanbul
Country [54] 0 0
Turkey
State/province [54] 0 0
Samsun
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Bristol
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Leicester
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Plymouth

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To demonstrate the benefit of isatuximab in combination with carfilzomib and dexamethasone in
the prolongation of Progression Free Survival (PFS) as compared to carfilzomib and
dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM) previously
treated with 1 to 3 lines of therapy.

Secondary Objectives:

- To evaluate the Overall Response Rate (ORR), rate of very good partial response (VGPR)
or better and complete response (CR) rate in both arms using International Myeloma
Working Group (IMWG) criteria.

- To evaluate rate of VGPR or better with minimal residual disease (MRD) negativity in
both arms using IMWG criteria.

- To evaluate the Overall Survival (OS) in both arms.

- To evaluate safety in both arms.

- To evaluate duration of response (DOR) in both arms.

- To evaluate the Time To Progression (TTP) in both arms.

- To evaluate the Second Progression Free Survival (PFS2) in both arms.

- To evaluate the Time to first response

- To evaluate the Time to best response

- To determine the Pharmacokinetic profile of isatuximab in combination with carfilzomib.

- To evaluate the immunogenicity of isatuximab in isatuximab arm.

- To assess disease-specific and generic health-related quality of life (HRQL), disease
and treatment-related symptoms, health state utility, and health status in both arms.
Trial website
https://clinicaltrials.gov/show/NCT03275285
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

Summary results
Other publications