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/show/NCT03319667




Registration number
NCT03319667
Ethics application status
Date submitted
18/09/2017
Date registered
24/10/2017
Date last updated
4/06/2020

Titles & IDs
Public title
Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant
Scientific title
A Phase 3 Randomized, Open-label, Multicenter Study Assessing the Clinical Benefit of Isatuximab (SAR650984) in Combination With Bortezomib (Velcade®), Lenalidomide (Revlimid®) and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma (NDMM) Not Eligible for Transplant
Secondary ID [1] 0 0
2017-002238-21
Secondary ID [2] 0 0
EFC12522
Universal Trial Number (UTN)
Trial acronym
IMROZ
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 - Bortezomib
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Acetaminophen (paracetamol) or equivalent
Treatment: Drugs - Ranitidine or equivalent
Treatment: Drugs - Diphenhydramine or equivalent

Experimental: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm - Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone
Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Active Comparator: Bortezomib/Lenalidomide/Dexamethasone = VRd arm - Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone
Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone

Other: Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm - 4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone


Treatment: Drugs: Isatuximab SAR650984
Pharmaceutical form: Solution for infusion
Route of administration: Intravenous (IV)

Treatment: Drugs: Bortezomib
Pharmaceutical form: Lyophilized powder for injection
Route of administration: Intravenous/Subcutaneous

Treatment: Drugs: Lenalidomide
Pharmaceutical form: Capsules
Route of administration: Oral

Treatment: Drugs: Dexamethasone
Pharmaceutical form: Tablets, ampoules or vials for injection
Route of administration: Oral/Intravenous

Treatment: Drugs: Acetaminophen (paracetamol) or equivalent
Pharmaceutical form: Tablets
Route of administration: Oral

Treatment: Drugs: Ranitidine or equivalent
Pharmaceutical form: Solution for injection
Route of administration: Intravenous

Treatment: Drugs: Diphenhydramine or equivalent
Pharmaceutical form: Solution for injection
Route of administration: Intravenous

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival (PFS) - PFS defined as the time from the date of randomization to the date of first documentation of progression disease (PD) as determined by the independent review committee (IRC) or the date of death from any cause, whichever occurs first
Timepoint [1] 0 0
Up to approximately 60 months after the first patient in (FPI) or scheduled assessment
Secondary outcome [1] 0 0
Very good partial response (VGPR) or better rate - Proportion of patients with CR and VGPR as assessed by the IRC using the IMWG criteria
Timepoint [1] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [2] 0 0
Minimal residual disease (MRD) negativity rate - Proportion of patients for whom MRD measurement is negative
Timepoint [2] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [3] 0 0
Complete response rate (CR) - Proportion of patients with CR as assessed by the IRC using the IMWG criteria
Timepoint [3] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [4] 0 0
Overall response rate (ORR) - Proportion of patients with best overall response (BOR) recorded as CR, VGPR, or partial response (PR) as assessed by the IRC using the IMWG criteria
Timepoint [4] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [5] 0 0
Time to progression (TTP) - Defined as the time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria
Timepoint [5] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [6] 0 0
Duration of response (DOR) - Defined as the time from date of first IRC determined response to date of first IRC PD or death, whichever occurs first for patients achieving CR, VGPR, or PR
Timepoint [6] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [7] 0 0
Time to first response (TT1R) - Time from randomization to the first IRC determined response (PR or better) that is subsequently confirmed
Timepoint [7] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [8] 0 0
PFS on next line of therapy (PFS2) - Defined as the time from randomization to second objective PD, or death from any cause, whichever occurs first
Timepoint [8] 0 0
At 4 years after cutoff for primary PFS analysis
Secondary outcome [9] 0 0
PFS in MRD negative patients - Defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever comes first in MRD negative patients
Timepoint [9] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [10] 0 0
Overall survival (OS) - Defined as the time from the date of randomization to death from any cause
Timepoint [10] 0 0
At 4 years after cutoff for primary PFS analysis
Secondary outcome [11] 0 0
Adverse Events - Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) including infusion associated reactions (IARs), second primary malignancies, laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination
Timepoint [11] 0 0
Up to 30 days after end of treatment (EOT) visit
Secondary outcome [12] 0 0
Assessment of PK parameter: Ctrough - Isatuximab: Pre-dose plasma isatuximab concentration (Ctrough)
Timepoint [12] 0 0
Cycle 1 Day 8/Day 15/Day 29 (pre-dose) and Day 1 (pre-dose) of Cycle 2, 3, 4, 5, 6, 7, 8, 9 and 10 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks)
Secondary outcome [13] 0 0
Assessment of PK parameter: AUC - Isatuximab: Cumulative area under the plasma isatuximab concentration versus time curve (AUC)
Timepoint [13] 0 0
Cycle 1 Day 1 to Day 29
Secondary outcome [14] 0 0
Assessment of PK parameter: CL - Isatuximab: Clearance (CL) for linear non-specific elimination pathway
Timepoint [14] 0 0
Cycle 1 Day 1 to Cycle 10 Day 1 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks)
Secondary outcome [15] 0 0
Immunogenicity - Levels of isatuximab anti-drug antibodies
Timepoint [15] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [16] 0 0
Patient reported outcome (PRO): QLQ-C30 - Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
Timepoint [16] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [17] 0 0
PRO: QLQ-MY20 - Disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ-MY20) questionnaire
Timepoint [17] 0 0
Up to approximately 60 months after the FPI or scheduled assessment
Secondary outcome [18] 0 0
PRO: EQ-5D-5L - Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Timepoint [18] 0 0
Up to approximately 60 months after the FPI or scheduled assessment

Eligibility
Key inclusion criteria
Inclusion criteria :

- Multiple myeloma (IMWG criteria).

- Newly diagnosed multiple myeloma not eligible for transplant due to age (= 65 years)
or patients < 65 years with comorbidities impacting possibility of transplant.

- Evidence of measurable disease.

- Written informed consent.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Age < 18 years.

- Prior treatment for multiple myeloma.

- Any other prior or ongoing disease/health conditions incompatible with the study
objectives.

- Organ function values not met.

- Eastern Cooperative Oncology Group (ECOG) Performance Status ( PS) > 2.

- Hypersensitivity to the study medications.

- Pregnant, breastfeeding, or woman of child bearing potential unwilling to use
recommended contraception methods.

- Male participants who disagree to follow the study contraceptive counseling.

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 - Clayton
Recruitment hospital [2] 0 0
Investigational Site Number 0360004 - Heidelberg West
Recruitment hospital [3] 0 0
Investigational Site Number 0360003 - Liverpool
Recruitment hospital [4] 0 0
Investigational Site Number 0360006 - Nedlands
Recruitment hospital [5] 0 0
Investigational Site Number 0360007 - South Brisbane
Recruitment hospital [6] 0 0
Investigational Site Number 0360001 - Waratah
Recruitment hospital [7] 0 0
Investigational Site Number 0360008 - West Perth
Recruitment hospital [8] 0 0
Investigational Site Number 0360002 - Wollongong
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
2298 - Waratah
Recruitment postcode(s) [7] 0 0
6005 - West Perth
Recruitment postcode(s) [8] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Liège
Country [6] 0 0
China
State/province [6] 0 0
Beijing
Country [7] 0 0
China
State/province [7] 0 0
Changchun
Country [8] 0 0
China
State/province [8] 0 0
Fuzhou
Country [9] 0 0
China
State/province [9] 0 0
Guangzhou
Country [10] 0 0
China
State/province [10] 0 0
Hangzhou
Country [11] 0 0
China
State/province [11] 0 0
Nanjing
Country [12] 0 0
China
State/province [12] 0 0
Shanghai
Country [13] 0 0
China
State/province [13] 0 0
Shenyang
Country [14] 0 0
China
State/province [14] 0 0
Tianjin
Country [15] 0 0
China
State/province [15] 0 0
Wuhan
Country [16] 0 0
Czechia
State/province [16] 0 0
Brno
Country [17] 0 0
Czechia
State/province [17] 0 0
Hradec Kralove
Country [18] 0 0
Czechia
State/province [18] 0 0
Olomouc
Country [19] 0 0
Czechia
State/province [19] 0 0
Ostrava - Poruba
Country [20] 0 0
Czechia
State/province [20] 0 0
Plzen
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha 2
Country [22] 0 0
Denmark
State/province [22] 0 0
Aalborg
Country [23] 0 0
Denmark
State/province [23] 0 0
Aarhus N
Country [24] 0 0
Denmark
State/province [24] 0 0
Odense C
Country [25] 0 0
France
State/province [25] 0 0
Bayonne
Country [26] 0 0
France
State/province [26] 0 0
Caen Cedex 9
Country [27] 0 0
France
State/province [27] 0 0
Dijon
Country [28] 0 0
France
State/province [28] 0 0
La Roche Sur Yon
Country [29] 0 0
France
State/province [29] 0 0
Lille
Country [30] 0 0
France
State/province [30] 0 0
Nantes
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
Pessac
Country [33] 0 0
France
State/province [33] 0 0
Pierre Benite Cedex
Country [34] 0 0
France
State/province [34] 0 0
Poitiers Cedex
Country [35] 0 0
France
State/province [35] 0 0
Toulouse Cedex 9
Country [36] 0 0
France
State/province [36] 0 0
Vandoeuvre-Les-Nancy Cedex
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Germany
State/province [38] 0 0
Frankfurt Am Main
Country [39] 0 0
Germany
State/province [39] 0 0
Heidelberg
Country [40] 0 0
Germany
State/province [40] 0 0
Tübingen
Country [41] 0 0
Greece
State/province [41] 0 0
Athens
Country [42] 0 0
Greece
State/province [42] 0 0
Thessaloniki
Country [43] 0 0
Italy
State/province [43] 0 0
Ancona
Country [44] 0 0
Italy
State/province [44] 0 0
Bergamo
Country [45] 0 0
Italy
State/province [45] 0 0
Bologna
Country [46] 0 0
Italy
State/province [46] 0 0
Brescia
Country [47] 0 0
Italy
State/province [47] 0 0
Torino
Country [48] 0 0
Japan
State/province [48] 0 0
Higashiibaraki-Gun
Country [49] 0 0
Japan
State/province [49] 0 0
Konan-Ku, Yokohama-Shi
Country [50] 0 0
Japan
State/province [50] 0 0
Kumamoto-Shi
Country [51] 0 0
Japan
State/province [51] 0 0
Nagoya-Shi
Country [52] 0 0
Japan
State/province [52] 0 0
Okayama-Shi
Country [53] 0 0
Japan
State/province [53] 0 0
Sendai-Shi
Country [54] 0 0
Japan
State/province [54] 0 0
Shibuya-Ku
Country [55] 0 0
Japan
State/province [55] 0 0
Shinjuku-Ku
Country [56] 0 0
Japan
State/province [56] 0 0
Sunto-Gun
Country [57] 0 0
Japan
State/province [57] 0 0
Yamagata-Shi
Country [58] 0 0
Lithuania
State/province [58] 0 0
Klaipeda
Country [59] 0 0
Lithuania
State/province [59] 0 0
Vilnius
Country [60] 0 0
Mexico
State/province [60] 0 0
Monterrey
Country [61] 0 0
New Zealand
State/province [61] 0 0
Auckland
Country [62] 0 0
New Zealand
State/province [62] 0 0
Hamilton
Country [63] 0 0
New Zealand
State/province [63] 0 0
Takapuna
Country [64] 0 0
Poland
State/province [64] 0 0
Gdansk
Country [65] 0 0
Poland
State/province [65] 0 0
Lodz
Country [66] 0 0
Poland
State/province [66] 0 0
Poznan
Country [67] 0 0
Poland
State/province [67] 0 0
Warszawa
Country [68] 0 0
Portugal
State/province [68] 0 0
Braga
Country [69] 0 0
Portugal
State/province [69] 0 0
Coimbra
Country [70] 0 0
Portugal
State/province [70] 0 0
Lisboa
Country [71] 0 0
Portugal
State/province [71] 0 0
Porto
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Moscow
Country [73] 0 0
Spain
State/province [73] 0 0
Barcelona
Country [74] 0 0
Spain
State/province [74] 0 0
Madrid
Country [75] 0 0
Spain
State/province [75] 0 0
Murcia
Country [76] 0 0
Sweden
State/province [76] 0 0
Lund
Country [77] 0 0
Sweden
State/province [77] 0 0
Stockholm
Country [78] 0 0
Taiwan
State/province [78] 0 0
Changhua
Country [79] 0 0
Taiwan
State/province [79] 0 0
Taichung
Country [80] 0 0
Taiwan
State/province [80] 0 0
Taipei
Country [81] 0 0
Turkey
State/province [81] 0 0
Adana
Country [82] 0 0
Turkey
State/province [82] 0 0
Ankara
Country [83] 0 0
Turkey
State/province [83] 0 0
Istanbul
Country [84] 0 0
Turkey
State/province [84] 0 0
Izmir
Country [85] 0 0
Turkey
State/province [85] 0 0
Kayseri
Country [86] 0 0
Turkey
State/province [86] 0 0
Samsun

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 (I) in combination with bortezomib (V), lenalidomide
(R) and dexamethasone (d) in the prolongation of progression free survival (PFS) as compared
with bortezomib, lenalidomide and dexamethasone in patients with newly diagnosed multiple
myeloma (NDMM) not eligible for transplant.

Secondary Objectives:

- To evaluate in both randomized arms: very good partial response (VGPR) or better rate as
defined by the International Myeloma Working Group (IMWG) criteria, minimal residual
disease (MRD) negativity rate in patients with complete response (CR) or VGPR, CR rate
per IMWG criteria, time to progression (TTP) and overall by MRD status, PFS in MRD
negative patients, duration of response (DOR) and overall by MRD status, time to first
response (TT1R), PFS on next line of therapy (PFS2), overall survival (OS), overall
response rate (ORR) (including crossover arm) per IMWG criteria (including crossover
arm), safety (including crossover arm), and to assess disease-specific and generic
health-related quality of life (HRQL)

- To determine the pharmacokinetic (PK) profile of isatuximab in combination with
bortezomib, lenalidomide, and dexamethasone (excluding crossover arm)

- To evaluate the immunogenicity of isatuximab in patients receiving isatuximab (including
crossover arm)
Trial website
https://clinicaltrials.gov/show/NCT03319667
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