A Study to Investigate the Clinical Benefit of Isatuximab in Combination With Bortezomib, Lenalidomide and Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

NCT03319667 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: EFC12522U1111-1194-21212024-514417-342017-002238-21
• Study Type: interventional
• Target: 475
• Locations: 21 countries
• Sites: 104

Brief Summary

Primary Objective:

• To demonstrate the benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone in the prolongation of progression free survival (PFS) as compared to bortezomib, lenalidomide, and dexamethasone, in participants with newly diagnosed multiple myeloma (NDMM) not eligible for transplant. Secondary Objectives:
• To evaluate in both randomized (isatuximab, bortezomib, lenalidomide and dexamethasone combination (IVRd) and bortezomib, lenalidomide and dexamethasone combination (VRd)) arms:
• Complete response (CR) rate, as defined by the International Myeloma Working Group (IMWG) criteria.
• Minimal residual disease (MRD) negativity rate in participants with CR.
• Very good partial response or better rate, as defined by the IMWG criteria.
• Overall survival (OS).
• To evaluate the overall response rate (ORR) as per IMWG criteria.
• To evaluate the time to progression (TTP) overall and by MRD status.
• To evaluate PFS by MRD status.
• To evaluate the duration of response (DOR) overall and by MRD status.
• To evaluate time to first response (TT1R).
• To evaluate time to best response (TTBR).
• To evaluate progression-free survival on next line of therapy (PFS2).
• To evaluate the sustained MRD negativity \>12 months rate.
• To evaluate safety.
• To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only).
• To evaluate the immunogenicity of isatuximab in participants receiving isatuximab (IVRd and crossover arms).
• To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Progression free survival (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.

  Up to approximately 100 months after the First Participant In (FPI)

Secondary Outcomes (18)

• Complete response rate (CR)

  Up to approximately 100 months after the FPI

• Minimal residual disease (MRD) negativity rate for participants with CR

  Up to approximately 100 months after the FPI

• Very good partial response (VGPR) or better rate

  Up to approximately 100 months after the FPI

• Overall survival (OS)

  Up to approximately 110 months after the FPI

• Overall response rate (ORR)

  Up to approximately 100 months after the FPI assessment

Study Arms (3)

Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm

EXPERIMENTAL

1. Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Drug: Isatuximab SAR650984; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Bortezomib/Lenalidomide/Dexamethasone = VRd arm

ACTIVE COMPARATOR

1. Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone

Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm

OTHER

4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Drug: Isatuximab SAR650984; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Isatuximab SAR650984 DRUG

Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV)

Also known as: Sarclisa

Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm; Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm

Bortezomib DRUG

Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous

Also known as: Velcade®

Bortezomib/Lenalidomide/Dexamethasone = VRd arm; Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm

Lenalidomide DRUG

Pharmaceutical form: Capsules Route of administration: Oral

Bortezomib/Lenalidomide/Dexamethasone = VRd arm; Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm; Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm

Dexamethasone DRUG

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

Bortezomib/Lenalidomide/Dexamethasone = VRd arm; Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm; Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple myeloma (IMWG criteria).
• Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or participants \< 65 years with comorbidities impacting possibility of transplant.
• Evidence of measurable disease.
• Written informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (104)

Investigational Site Number: 8400006

Fort Myers, Florida, 33901, United States

Location

Investigational Site Number: 8400004

St. Petersburg, Florida, 33705, United States

Location

Investigational Site Number: 8400007

Kansas City, Missouri, 64132, United States

Location

Investigational Site Number: 8400005

Nashville, Tennessee, 37203, United States

Location

Investigational Site Number: 8400001

Houston, Texas, 77030, United States

Location

Investigational Site Number : 0360003

Liverpool, New South Wales, 2170, Australia

Location

Investigational Site Number : 0360001

Waratah, New South Wales, 2298, Australia

Location

Investigational Site Number : 0360002

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number : 0360007

South Brisbane, Queensland, 4101, Australia

Location

Investigational Site Number : 0360005

Clayton, Victoria, 3168, Australia

Location

Investigational Site Number : 0360004

Heidelberg West, Victoria, 3081, Australia

Location

Investigational Site Number : 0360006

Nedlands, Western Australia, 6009, Australia

Location

Investigational Site Number : 0360008

West Perth, Western Australia, 6005, Australia

Location

Investigational Site Number : 0560001

Liège, 4000, Belgium

Location

Investigational Site Number : 1560002

Beijing, 100034, China

Location

Investigational Site Number : 1560003

Beijing, 100191, China

Location

Investigational Site Number : 1560008

Changchun, 130021, China

Location

Investigational Site Number : 1560007

Fuzhou, 350001, China

Location

Investigational Site Number : 1560009

Guangzhou, 510060, China

Location

Investigational Site Number : 1560006

Guangzhou, 510080, China

Location

Investigational Site Number : 1560005

Hangzhou, 310003, China

Location

Investigational Site Number : 1560014

Hangzhou, 310003, China

Location

Investigational Site Number : 1560004

Nanjing, 210029, China

Location

Investigational Site Number : 1560013

Shanghai, 200025, China

Location

Investigational Site Number : 1560011

Shenyang, 110022, China

Location

Investigational Site Number : 1560001

Tianjin, 300020, China

Location

Investigational Site Number : 1560012

Wuhan, 430022, China

Location

Investigational Site Number : 2030002

Brno, 62500, Czechia

Location

Investigational Site Number : 2030007

Hradec Králové, 50005, Czechia

Location

Investigational Site Number : 2030004

Olomouc, 77900, Czechia

Location

Investigational Site Number : 2030003

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number : 2030006

Pilsen, 30599, Czechia

Location

Investigational Site Number : 2030001

Prague, 12808, Czechia

Location

Investigational Site Number : 2080002

Aalborg, 9000, Denmark

Location

Investigational Site Number : 2080003

Aarhus N, 8200, Denmark

Location

Investigational Site Number : 2080004

Odense C, 5000, Denmark

Location

Investigational Site Number : 2500011

Bayonne, 64100, France

Location

Investigational Site Number : 2500007

Caen, 14033, France

Location

Investigational Site Number : 2500009

Dijon, 21000, France

Location

Investigational Site Number : 2500008

La Roche-sur-Yon, 85925, France

Location

Investigational Site Number : 2500001

Lille, 59037, France

Location

Investigational Site Number : 2500003

Nantes, 44093, France

Location

Investigational Site Number : 2500012

Paris, 75012, France

Location

Investigational Site Number : 2500002

Pessac, 33600, France

Location

Investigational Site Number : 2500006

Pierre-Bénite, 69495, France

Location

Investigational Site Number : 2500005

Poitiers, 86021, France

Location

Investigational Site Number : 2500004

Toulouse, 31059, France

Location

Investigational Site Number : 2500010

Vandœuvre-lès-Nancy, 54511, France

Location

Investigational Site Number : 2760003

Berlin, 13125, Germany

Location

Investigational Site Number : 2760004

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number : 2760001

Heidelberg, 69120, Germany

Location

Investigational Site Number : 2760005

Tübingen, 72076, Germany

Location

Investigational Site Number : 3000003

Athens, 10676, Greece

Location

Investigational Site Number : 3000001

Athens, 11528, Greece

Location

Investigational Site Number : 3000002

Thessaloniki, 57010, Greece

Location

Investigational Site Number : 3800005

Ancona, 60032, Italy

Location

Investigational Site Number : 3800003

Bergamo, 24127, Italy

Location

Investigational Site Number : 3800001

Bologna, 40138, Italy

Location

Investigational Site Number : 3800004

Brescia, 25123, Italy

Location

Investigational Site Number : 3800002

Torino, 10126, Italy

Location

Investigational Site Number : 3920007

Nagoya, Aichi-ken, 467-8602, Japan

Location

Investigational Site Number : 3920004

Higashiibaraki-gun, Ibaraki, 311-3193, Japan

Location

Investigational Site Number : 3920008

Konan-ku, Yokohama-shi, Kanagawa, 234-0054, Japan

Location

Investigational Site Number : 3920003

Kumamoto, Kumamoto, 860-8556, Japan

Location

Investigational Site Number : 3920009

Sendai, Miyagi, 983-8520, Japan

Location

Investigational Site Number : 3920005

Okayama, Okayama-ken, 701-1192, Japan

Location

Investigational Site Number : 3920006

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Investigational Site Number : 3920001

Shibuya-ku, Tokyo, 150-8935, Japan

Location

Investigational Site Number : 3920002

Shinjuku-ku, Tokyo, 162-8666, Japan

Location

Investigational Site Number : 3920010

Yamagata, 990-9585, Japan

Location

Investigational Site Number : 4400002

Klaipėda, LT-92288, Lithuania

Location

Investigational Site Number : 4400001

Vilnius, 08661, Lithuania

Location

Investigational Site Number : 4840001

Monterrey, Nuevo León, 64460, Mexico

Location

Investigational Site Number : 5540002

Takapuna, Auckland, 1309, New Zealand

Location

Investigational Site Number : 5540003

Hamilton, Waikato Region, 3204, New Zealand

Location

Investigational Site Number : 5540001

Auckland, 2025, New Zealand

Location

Investigational Site Number : 6160004

Poznan, Greater Poland Voivodeship, 60-631, Poland

Location

Investigational Site Number : 6160003

Lodz, Lódzkie, 93-510, Poland

Location

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Investigational Site Number : 6160002

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Investigational Site Number : 6200002

Braga, 4710-243, Portugal

Location

Investigational Site Number : 6200006

Coimbra, 3000-075, Portugal

Location

Investigational Site Number : 6200001

Lisbon, 1070, Portugal

Location

Investigational Site Number : 6200005

Porto, 4200-319, Portugal

Location

Investigational Site Number : 6200003

Porto, 4200, Portugal

Location

Investigational Site Number : 6430001

Moscow, 125284, Russia

Location

Investigational Site Number : 6430002

Moscow, 129301, Russia

Location

Investigational Site Number : 7240005

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240004

Barcelona, Barcelona [Barcelona], 08041, Spain

Location

Investigational Site Number : 7240003

Madrid, 28034, Spain

Location

Investigational Site Number : 7240001

Murcia, 30008, Spain

Location

Investigational Site Number : 7520002

Lund, 221 85, Sweden

Location

Investigational Site Number : 7520001

Stockholm, 14186, Sweden

Location

Investigational Site Number : 1580003

Changhua, 500, Taiwan

Location

Investigational Site Number : 1580002

Taichung, 40447, Taiwan

Location

Investigational Site Number : 1580001

Taipei, 100, Taiwan

Location

Investigational Site Number : 7920006

Adana, 01250, Turkey (Türkiye)

Location

Investigational Site Number : 7920007

Ankara, 06500, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Ankara, 06620, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Istanbul, 34390, Turkey (Türkiye)

Location

Investigational Site Number : 7920004

Izmir, 35040, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Izmir, 35340, Turkey (Türkiye)

Location

Investigational Site Number : 7920005

Kayseri, 38039, Turkey (Türkiye)

Location

Investigational Site Number : 7920008

Samsun, 55139, Turkey (Türkiye)

Location

Related Publications (4)

• Orlowski RZ, Dimopoulos MA, Leleu X, Facon T, Ishida T, Hajek R, Spicka I, Romejko-Jarosinska J, Vorobyev VI, Besemer B, Kalayoglu Besisik S, Robak P, Jelinek T, Goldschmidt H, Martin T, Mohty M, Mace S, Kodas E, Tekle C, Shafer AT, Moreau P. Isatuximab, bortezomib, lenalidomide, dexamethasone for multiple myeloma: dynamics of MRD-negativity in the IMROZ study. Blood. 2026 Feb 27:blood.2025030120. doi: 10.1182/blood.2025030120. Online ahead of print.

  PMID: 41758929 DERIVED

• Manier S, Dimopoulos MA, Leleu XP, Moreau P, Cavo M, Goldschmidt H, Orlowski RZ, Tron M, Tekle C, Bregeault MF, Shafer AT, Beksac M, Facon T. Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial. Haematologica. 2025 Sep 1;110(9):2139-2150. doi: 10.3324/haematol.2024.287200. Epub 2025 Mar 20.

  PMID: 40109195 DERIVED

• Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hajek R, Liu Z, Minarik J, Moreau P, Romejko-Jarosinska J, Spicka I, Vorobyev VI, Besemer B, Ishida T, Janowski W, Kalayoglu-Besisik S, Parmar G, Robak P, Zamagni E, Goldschmidt H, Martin TG, Manier S, Mohty M, Oprea C, Bregeault MF, Mace S, Berthou C, Bregman D, Klippel Z, Orlowski RZ; IMROZ Study Group. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Oct 31;391(17):1597-1609. doi: 10.1056/NEJMoa2400712. Epub 2024 Jun 3.

  PMID: 38832972 DERIVED

• Thoren K, Menad S, Nouadje G, Mace S. Isatuximab-Specific Immunofixation Electrophoresis Assay to Remove Interference in Serum M-Protein Measurement in Patients with Multiple Myeloma. J Appl Lab Med. 2024 Jul 1;9(4):661-671. doi: 10.1093/jalm/jfae028.

  PMID: 38573925 DERIVED

Related Links

• EFC12522 Plain Language Results Summary

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; Bortezomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel and crossover

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: October 24, 2017
• Study Start: December 7, 2017
• Primary Completion (Estimated): April 5, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

RU (2); BE (1); DE (4); AU (8); CZ (6); IT (5); ME (1); ES (4); JP (10); TW (3); TU (8); DK (3); PT (5); FR (12); GR (3); CN (13); LI (2); PL (4); SE (2); NZ (3); US (5)