Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients

NCT03275285 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC15246U1111-1195-59572017-001940-37
• Study Type: interventional
• Target: 302
• Locations: 16 countries
• Sites: 70

Brief Summary

The purpose of this study it to compare the efficacity of isatuximab when combined to carfilzomib and dexamethasone versus carfilzomib and dexamethasone in patients with multiple myeloma already treated with 1 to 3 prior lines of therapy.

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (4)

• Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis

  Time (in months) from randomization to date of 1st documentation of progressive disease (PD)/date of death from any cause, whichever comes 1st. If PD \& death are not observed before cut-off date/date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment not showing PD performed prior to initiation of further anti-myeloma treatment/cut-off date, whichever comes 1st. PD(IMWG criteria):any 1 of following:Increase(inc) of \>=25% in serum M-component from nadir; serum M component inc \>=1 g/dL in 2 consecutive assessment, if starting M component \>=5 g/dL; and/or inc of \>=25% in urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc \>=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion if \>1 lesion/ \>=50% increase in longest diameter of previous soft tissue extramedullary disease lesion \>1 cm in short axis. Estimated by Kaplan-Meier method.

  From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months)

• Progression Free Survival as Determined by Independent Response Committee: [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Primary Analysis

  Time (in months) from randomization to date of 1st PD documentation/death date, whichever is 1st. If PD \& death not observed before cut-off date/date of further anti-myeloma treatment initiation, PFS censored at date of last valid disease assessment not showing PD performed prior to initiation of further anti-myeloma treatment/cut-off date, whichever was 1st. Progression/deaths occurring \>8 weeks after last disease assessment censored at earliest date of last disease assessment without evidence of progression before initiation of new anti-myeloma treatment \& cut-off date. PD (IMWG criteria): meeting any 1: Inc \>=25% in Serum M-component from nadir; serum M component inc \>=1 g/dL in 2 consecutive assessment, if starting M component \>=5 g/dL; and/or inc \>=25% in Urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc \>=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion \>1 cm short axis.

  From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

• Progression Free Survival as Determined by Independent Response Committee: Final Analysis

  PFS: time (in months) from randomization to date of first documentation of PD or date of death from any cause, whichever comes first. If PD and death are not observed before analysis cut-off date or date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment or analysis cut-off date, whichever comes first. PD as per IMWG criteria: any 1 of following: Inc of \>=25% in Serum M-component from nadir; serum M component increase \>=1 g/dL in 2 consecutive assessment, if starting M component was \>=5 g/dL; and/or inc of \>=25% in Urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc \>=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion if \>1 lesion/ \>=50% inc in longest diameter of previous soft tissue extramedullary disease lesion \>1 cm in short axis. PFS estimated by Kaplan-Meier method.

  From randomization until the final analysis data cut-off date of 14 January 2022 (the median duration of follow-up was 43.96 months)

• Progression Free Survival as Determined by Independent Response Committee [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Final Analysis

  Time (in months) from randomization to date of 1st documentation of PD/date of death from any cause, whichever comes 1st. If PD \& death are not observed before cut-off date/date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment not showing PD/cut-off date, whichever comes 1st. Progressions/deaths occurring \>8 weeks after last disease assessment were censored at earliest date of last valid disease assessment not showing PD before initiation of further anti-myeloma treatment \& cut-off date. PD (per IMWG criteria): meeting any 1 criteria: Inc of \>=25% in serum M-component from nadir; serum M component inc \>=1 g/dL in 2 consecutive assessment, if starting M component was \>=5 g/dL; and/or inc of \>=25% in urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc \>=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion \>1 cm in short axis.

  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 Outcomes (35)

• Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis

  From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

• Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis

  From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

• Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis

  From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

• Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Final Analysis

  From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

• Percentage of Participants With Complete Response (CR) as Per Independent Response Committee: Final Analysis

  From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

Study Arms (2)

Isatuximab + Carfilzomib + Dexamethasone (IKd)

EXPERIMENTAL

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.

Drug: isatuximab SAR650984; Drug: carfilzomib; Drug: dexamethasone

Carfilzomib + Dexamethasone (Kd)

ACTIVE COMPARATOR

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.

Drug: carfilzomib; Drug: dexamethasone

Interventions

carfilzomib DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: Kyprolis

Carfilzomib + Dexamethasone (Kd); Isatuximab + Carfilzomib + Dexamethasone (IKd)

dexamethasone DRUG

Pharmaceutical form: tablets or solution for infusion Route of administration: oral or intravenous

Carfilzomib + Dexamethasone (Kd); Isatuximab + Carfilzomib + Dexamethasone (IKd)

isatuximab SAR650984 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: Sarclisa

Isatuximab + Carfilzomib + Dexamethasone (IKd)

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (70)

UCSF MS Center Site Number : 8400002

San Francisco, California, 94117, United States

Location

Spartanburg Medical Center Site Number : 8400003

Spartanburg, South Carolina, 29303-3040, United States

Location

Investigational Site Number : 0360005

Blacktown, New South Wales, 2148, Australia

Location

Investigational Site Number : 0360006

Tweed Heads, New South Wales, 2485, Australia

Location

Investigational Site Number : 0360002

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number : 0360001

Fitzroy, Victoria, 3065, Australia

Location

Investigational Site Number : 0360004

Heidelberg West, Victoria, 3081, Australia

Location

Investigational Site Number : 0360007

Nedlands, Western Australia, 6009, Australia

Location

Investigational Site Number : 0360008

West Perth, Western Australia, 6005, Australia

Location

Hospital Sao Rafael - Rede D'OR Sao Luiz Site Number : 0760005

Salvador, Estado de Bahia, 41253-900, Brazil

Location

Hospital Mae de Deus Site Number : 0760003

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Hospital de Amor - Hospital do Cancer de Barretos - Fundacao Pio XII Site Number : 0760001

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital das Clinicas de Sao Paulo Site Number : 0760002

São Paulo, São Paulo, 05403-000, Brazil

Location

Instituto COI de Educacao e Pesquisa Site Number : 0760004

Rio de Janeiro, 22775-002, Brazil

Location

Investigational Site Number : 1240003

Surrey, British Columbia, V3V 1Z2, Canada

Location

Investigational Site Number : 1240001

Saint John, New Brunswick, E2L 4L2, Canada

Location

Investigational Site Number : 1240002

Montreal, Quebec, H1T 2M4, Canada

Location

Investigational Site Number : 2030002

Brno, 62500, Czechia

Location

Investigational Site Number : 2030004

Olomouc, 77900, Czechia

Location

Investigational Site Number : 2030003

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number : 2030001

Prague, 12808, Czechia

Location

Investigational Site Number : 2500003

Lille, 59037, France

Location

Investigational Site Number : 2500001

Nantes, 44093, France

Location

Investigational Site Number : 2500006

Paris, 75012, France

Location

Investigational Site Number : 2500002

Pessac, 33600, France

Location

Investigational Site Number : 2500005

Pierre-Bénite, 69495, France

Location

Investigational Site Number : 2500004

Poitiers, 86021, France

Location

Investigational Site Number : 3000002

Athens, 10676, Greece

Location

Investigational Site Number : 3000005

Athens, 11527, Greece

Location

Investigational Site Number : 3000001

Athens, 11528, Greece

Location

Investigational Site Number : 3000004

Pátrai, 26504, Greece

Location

Investigational Site Number : 3000003

Thessaloniki, 57010, Greece

Location

Investigational Site Number : 3480003

Budapest, 1083, Hungary

Location

Investigational Site Number : 3480001

Budapest, 1097, Hungary

Location

Investigational Site Number : 3480004

Budapest, 1125, Hungary

Location

Investigational Site Number : 3480005

Kaposvár, 7400, Hungary

Location

Investigational Site Number : 3800003

Bologna, 40138, Italy

Location

Investigational Site Number : 3800001

Pisa, 56126, Italy

Location

Investigational Site Number : 3800004

Reggio Emilia, 42123, Italy

Location

Investigational Site Number : 3800002

Torino, 10126, Italy

Location

Investigational Site Number : 3920005

Shiwa-gun, Iwate, 028-3695, Japan

Location

Investigational Site Number : 3920007

Kumamoto, Kumamoto, 860-8556, Japan

Location

Investigational Site Number : 3920001

Suwa-shi, Nagano, 392-8510, Japan

Location

Investigational Site Number : 3920003

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Investigational Site Number : 3920004

Shibuya-ku, Tokyo, 150-8935, Japan

Location

Investigational Site Number : 3920006

Shinjuku-ku, Tokyo, 162-8666, Japan

Location

Investigational Site Number : 3920002

Yamagata, 990-9585, Japan

Location

Investigational Site Number : 5540001

Auckland, 1640, New Zealand

Location

Investigational Site Number : 5540002

Wellington, 6021, New Zealand

Location

Investigational Site Number : 6430003

Kirov, 610027, Russia

Location

Investigational Site Number : 6430004

Novosibirsk, 630047, Russia

Location

Investigational Site Number : 6430002

Yekaterinburg, 620102, Russia

Location

Investigational Site Number : 4100006

Busan, Busan, 602-715, South Korea

Location

Investigational Site Number : 4100002

Gangnam-gu, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 4100005

Seoul, 06591, South Korea

Location

Investigational Site Number : 7240001

Badalona, Catalunya [Cataluña], 08916, Spain

Location

Investigational Site Number : 7240005

Barcelona, Catalunya [Cataluña], 08036, Spain

Location

Investigational Site Number : 7240002

Valencia, Valenciana, Comunidad, 46017, Spain

Location

Investigational Site Number : 7240003

Madrid, 28041, Spain

Location

Investigational Site Number : 7240004

Seville, 41013, Spain

Location

Investigational Site Number : 7920003

Adana, 01250, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Ankara, 06500, Turkey (Türkiye)

Location

Investigational Site Number : 7920005

Bursa, 16059, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Istanbul, 34381, Turkey (Türkiye)

Location

Investigational Site Number : 7920004

Samsun, 55139, Turkey (Türkiye)

Location

Investigational Site Number : 8260004

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Investigational Site Number : 8260005

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

Investigational Site Number : 8260001

Bristol, Somerset, BS2 8ED, United Kingdom

Location

Related Publications (10)

• Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Spicka I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Mace S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. doi: 10.1016/S0140-6736(21)00592-4. Epub 2021 Jun 4.

  PMID: 34097854 RESULT

• Martin TG, Capra M, Mohty M, Suzuki K, Quach H, Cavo M, Moreau P, Dimopoulos M, Yong K, Tekle C, Foster MC, Barnes Y, Risse ML, Mikhael J. Isatuximab Plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: IKEMA Subgroup Analysis by Prior Transplantation. Transplant Cell Ther. 2023 Feb;29(2):134.e1-134.e7. doi: 10.1016/j.jtct.2022.11.005. Epub 2022 Nov 11.

  PMID: 36372355 RESULT

• Chami B, Okuda M, Moayeri M, Pirenne F, Hidaka Y, Nambiar A, Song Z, Bedel O, Zhang B, Hopke J, Deng G, Zhu C, Mace S, Chiron M, Adrian F, Fukao T, Basile FG, Martin T. Anti-CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping. Transfusion. 2022 Nov;62(11):2334-2348. doi: 10.1111/trf.17137. Epub 2022 Oct 14.

  PMID: 36239134 RESULT

• Yong K, Martin T, Dimopoulos MA, Mikhael J, Capra M, Facon T, Hajek R, Spicka I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Casca F, Mace S, Risse ML, Moreau P. Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial. Lancet Haematol. 2024 Oct;11(10):e741-e750. doi: 10.1016/S2352-3026(24)00148-0. Epub 2024 Jul 24.

  PMID: 39067465 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

• Facon T, Moreau P, Baker R, Min CK, Leleu X, Mohty M, Karlin L, Armstrong NM, Tekle C, Schwab S, Risse ML, Martin T. Isatuximab plus carfilzomib and dexamethasone in patients with early versus late relapsed multiple myeloma: IKEMA subgroup analysis. Haematologica. 2024 Feb 1;109(2):604-616. doi: 10.3324/haematol.2023.283073.

  PMID: 37584290 DERIVED

• Kawano Y, Kim K, Min CK, Koh Y, Ishizawa K, Kim SH, Ito S, Tanaka J, Uchiyama M, Ishida T, Kim JS, Moreau P, Martin T, Tada K, Risse ML, Suzuki K. Isatuximab Plus Carfilzomib and Dexamethasone in East Asian Patients With Relapsed Multiple Myeloma: Updated IKEMA Subgroup Analysis. Clin Lymphoma Myeloma Leuk. 2023 Oct;23(10):e360-e367. doi: 10.1016/j.clml.2023.06.011. Epub 2023 Jul 3.

  PMID: 37479547 DERIVED

• Martin T, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Spicka I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Casca F, Mace S, Risse ML, Moreau P. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Blood Cancer J. 2023 May 9;13(1):72. doi: 10.1038/s41408-023-00797-8.

  PMID: 37156782 DERIVED

• Beksac M, Spicka I, Hajek R, Bringhen S, Jelinek T, Martin T, Mikala G, Moreau P, Symeonidis A, Rawlings AM, van de Velde H, Richardson PG. Evaluation of isatuximab in patients with soft-tissue plasmacytomas: An analysis from ICARIA-MM and IKEMA. Leuk Res. 2022 Nov;122:106948. doi: 10.1016/j.leukres.2022.106948. Epub 2022 Sep 6.

  PMID: 36108425 DERIVED

• Moreau P, Dimopoulos MA, Yong K, Mikhael J, Risse ML, Asset G, Martin T. Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design. Future Oncol. 2020 Jan;16(2):4347-4358. doi: 10.2217/fon-2019-0431. Epub 2019 Dec 13.

  PMID: 31833394 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; carfilzomib; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: October 25, 2017
• Primary Completion: January 14, 2022
• Study Completion: January 3, 2025
• Last Updated: February 9, 2026
• Results First Posted: February 13, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

JP (7); TU (5); GB (3); IT (4); CZ (4); GR (5); US (2); RU (3); CA (3); NZ (2); KR (5); ES (5); AU (7); BR (5); HU (4); FR (6)