Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients

NCT ID: NCT02990338

Last Updated: 2025-01-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

307 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-22

Study Completion Date

2023-11-01

Brief Summary

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Primary Objective:

To demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to pomalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory multiple myeloma (MM).

Secondary Objectives:

* To evaluate the Overall Response Rate (ORR) as per International Myeloma Working Group (IMWG) criteria in each arm.
* To compare the Overall Survival (OS) between the two arms.
* To evaluate the Time To Progression (TTP) in each arm.
* To evaluate the PFS in high risk cytogenetic population in each arm.
* To evaluate the Duration of Response (DOR) in each arm.
* To evaluate the safety in both treatment arms.
* To determine the Pharmacokinetic profile of isatuximab in combination with pomalidomide.
* To evaluate the immunogenicity of isatuximab.
* To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

Detailed Description

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The duration of the study for the participants included a period for screening of up to 21 days (or up to 28 days for women who can become pregnant). Participants continued study treatment until disease progression, unacceptable adverse reaction, participants' wish or other reason of discontinuation.

During follow-up, participants who discontinued the study treatment due to progression of the disease were followed every 3 months (12 weeks) for survival (or until cut-off date), and participants who discontinued the study treatment prior to documentation of disease progression were followed-up every 4 weeks until disease progression, and then every 3 months (12 weeks) for survival (or until cut-off date).

Conditions

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Plasma Cell Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pd (pomalidomide + dexamethasone)

Participants received pomalidomide 4 milligrams (mg) Per os (PO) on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants greater than or equal to (\>=) 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 306.6 weeks).

Group Type ACTIVE_COMPARATOR

Pomalidomide

Intervention Type DRUG

Pharmaceutical form: capsule Route of administration: oral

Dexamethasone

Intervention Type DRUG

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

IPd (isatuximab + pomalidomide + dexamethasone)

Participants received isatuximab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 311.0 weeks).

Group Type EXPERIMENTAL

Isatuximab

Intervention Type DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Pomalidomide

Intervention Type DRUG

Pharmaceutical form: capsule Route of administration: oral

Dexamethasone

Intervention Type DRUG

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

Interventions

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Isatuximab

Pharmaceutical form: solution for infusion Route of administration: intravenous

Intervention Type DRUG

Pomalidomide

Pharmaceutical form: capsule Route of administration: oral

Intervention Type DRUG

Dexamethasone

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

Intervention Type DRUG

Other Intervention Names

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SAR650984 Sarclisa POMALYST IMNOVID

Eligibility Criteria

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Inclusion Criteria

* Age superior or equal to 18 years or country's legal age of majority if the legal age was superior to 18 years old.
* Participants had a documented diagnosis of multiple myeloma with evidence of measurable disease i.e. serum M protein superior or equal to 0.5 grams per decilitre (g/dL) measured using serum protein immunoelectrophoresis and or urine M protein superior or equal to 200 mg per 24 hours measured using urine protein immunoelectrophoresis.
* Participants had received at least 2 prior lines of anti-myeloma therapy, which must include at least 2 consecutive cycles of lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) given alone or in combination.
* Participants had failed treatment with lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination (Intolerant, progression within 6 months after reaching Partial Response or better).
* Participants had progressed on or within 60 days after end of previous therapy before to study entry, i.e., refractory to the last line of treatment.

Exclusion Criteria

* Primary refractory multiple myeloma defined as participants who had never achieved at least a minimal response (MR) with any treatment during the disease course.
* Free Light Chain measurable disease only.
* Prior therapy with pomalidomide.
* Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone.
* Eastern Cooperative Oncology Group performance status superior to 2.
* Platelets inferior to 75 000 cells per microliter (mcL) if inferior to 50% of bone marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per mcL if superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion was not allowed within three days before the screening visit.
* Absolute neutrophil count inferior to 1000 per mcL (1\*10\^9/L).
* Creatinine clearance inferior to 30 mL per minute (Modification of Diet in Renal Disease \[MDRD\] Formula).
* Total bilirubin superior to 2\*ULN (Upper Limit of Normal).
* Corrected serum calcium superior to 14 milligrams per deciliter (mg/dL) (superior to 3.5 millimoles per liter (mmol/L).
* Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to 3\*ULN.
* Hypersensitivity to immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide) defined as any hypersensitivity reaction leading to stop IMiDs within the 2 first cycles or toxicity, which does meet intolerance definition.
* Hypersensitivity to dexamethasone, sucrose histidine (as base and hydrochloride salt), and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, or H2 blockers that would prohibit further treatment with these agents.
* Significant cardiac dysfunction; myocardial infarction within 12 months; unstable, poorly controlled angina pectoris.
* Pregnant or breastfeeding woman or female who intends to become pregnant during the participation in the study.
* Male participants who disagreed to practice true abstinence or disagreed to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and at least 3 or 5 months following study treatment discontinuation, even if he had undergone a successful vasectomy.
* All participants who disagreed to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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BRCR Medical Center Inc. Site Number : 8400002

Plantation, Florida, United States

Site Status

Dana Farber Site Number : 8400006

Boston, Massachusetts, United States

Site Status

Investigational Site Number : 0360004

St Leonards, New South Wales, Australia

Site Status

Investigational Site Number : 0360001

Waratah, New South Wales, Australia

Site Status

Investigational Site Number : 0360005

Melbourne, Victoria, Australia

Site Status

Investigational Site Number : 0360002

Melbourne, Victoria, Australia

Site Status

Investigational Site Number : 0360006

Richmond, Victoria, Australia

Site Status

Investigational Site Number : 0560003

Antwerp, , Belgium

Site Status

Investigational Site Number : 0560002

Brussels, , Belgium

Site Status

Investigational Site Number : 0560004

Ghent, , Belgium

Site Status

Investigational Site Number : 0560001

Leuven, , Belgium

Site Status

Investigational Site Number : 1240001

Montreal, Quebec, Canada

Site Status

Investigational Site Number : 1240004

Montreal, Quebec, Canada

Site Status

Investigational Site Number : 1240005

Sherbrooke, Quebec, Canada

Site Status

Investigational Site Number : 2030005

Brno, , Czechia

Site Status

Investigational Site Number : 2030004

Hradec Králové, , Czechia

Site Status

Investigational Site Number : 2030001

Olomouc, , Czechia

Site Status

Investigational Site Number : 2030002

Ostrava - Poruba, , Czechia

Site Status

Investigational Site Number : 2030003

Prague, , Czechia

Site Status

Investigational Site Number : 2080002

Aalborg, , Denmark

Site Status

Investigational Site Number : 2500021

Bayonne, , France

Site Status

Investigational Site Number : 2500008

Caen, , France

Site Status

Investigational Site Number : 2500009

Dijon, , France

Site Status

Investigational Site Number : 2500017

Grenoble, , France

Site Status

Investigational Site Number : 2500013

La Roche-sur-Yon, , France

Site Status

Investigational Site Number : 2500003

Lille, , France

Site Status

Investigational Site Number : 2500023

Limoges, , France

Site Status

Investigational Site Number : 2500019

Montpellier, , France

Site Status

Investigational Site Number : 2500002

Nantes, , France

Site Status

Investigational Site Number : 2500015

Paris, , France

Site Status

Investigational Site Number : 2500016

Paris, , France

Site Status

Investigational Site Number : 2500005

Pessac, , France

Site Status

Investigational Site Number : 2500004

Pierre-Bénite, , France

Site Status

Investigational Site Number : 2500007

Poitiers, , France

Site Status

Investigational Site Number : 2500025

Reims, , France

Site Status

Investigational Site Number : 2500014

Rennes, , France

Site Status

Investigational Site Number : 2500001

Toulouse, , France

Site Status

Investigational Site Number : 2500012

Tours, , France

Site Status

Investigational Site Number : 2500018

Vandœuvre-lès-Nancy, , France

Site Status

Investigational Site Number : 2760001

Leipzig, , Germany

Site Status

Investigational Site Number : 3000002

Athens, , Greece

Site Status

Investigational Site Number : 3000005

Athens, , Greece

Site Status

Investigational Site Number : 3000001

Athens, , Greece

Site Status

Investigational Site Number : 3000004

Pátrai, , Greece

Site Status

Investigational Site Number : 3000003

Thessaloniki, , Greece

Site Status

Investigational Site Number : 3480001

Budapest, , Hungary

Site Status

Investigational Site Number : 3480003

Budapest, , Hungary

Site Status

Investigational Site Number : 3480002

Debrecen, , Hungary

Site Status

Investigational Site Number : 3800001

Bologna, , Italy

Site Status

Investigational Site Number : 3800010

Catania, , Italy

Site Status

Investigational Site Number : 3800009

Florence, , Italy

Site Status

Investigational Site Number : 3800008

Genova, , Italy

Site Status

Investigational Site Number : 3800007

Milan, , Italy

Site Status

Investigational Site Number : 3800002

Milan, , Italy

Site Status

Investigational Site Number : 3800006

Padua, , Italy

Site Status

Investigational Site Number : 3800004

Terni, , Italy

Site Status

Investigational Site Number : 3800003

Torino, , Italy

Site Status

Investigational Site Number : 3920001

Nagoya, Aichi-ken, Japan

Site Status

Investigational Site Number : 3920005

Shibukawa-shi, Gunma, Japan

Site Status

Investigational Site Number : 3920004

Sapporo, Hokkaido, Japan

Site Status

Investigational Site Number : 3920006

Kyoto, Kyoto, Japan

Site Status

Investigational Site Number : 3920008

Suwa-shi, Nagano, Japan

Site Status

Investigational Site Number : 3920003

Okayama, Okayama-ken, Japan

Site Status

Investigational Site Number : 3920007

Sunto-gun, Shizuoka, Japan

Site Status

Investigational Site Number : 3920002

Shibuya-ku, Tokyo, Japan

Site Status

Investigational Site Number : 5540001

Takapuna, Auckland, New Zealand

Site Status

Investigational Site Number : 5540004

Dunedin, Otago, New Zealand

Site Status

Investigational Site Number : 5540003

Hamilton, Waikato Region, New Zealand

Site Status

Investigational Site Number : 5540002

Auckland, , New Zealand

Site Status

Investigational Site Number : 5780001

Oslo, , Norway

Site Status

Investigational Site Number : 6160005

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Investigational Site Number : 6160003

Lublin, Lubusz Voivodeship, Poland

Site Status

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, Poland

Site Status

Investigational Site Number : 6160002

Chorzów, Silesian Voivodeship, Poland

Site Status

Investigational Site Number : 6200004

Coimbra, , Portugal

Site Status

Investigational Site Number : 6200002

Lisbon, , Portugal

Site Status

Investigational Site Number : 6200001

Porto, , Portugal

Site Status

Investigational Site Number : 6430004

Moscow, , Russia

Site Status

Investigational Site Number : 6430001

Moscow, , Russia

Site Status

Investigational Site Number : 6430002

Moscow, , Russia

Site Status

Investigational Site Number : 7030001

Bratislava, , Slovakia

Site Status

Investigational Site Number : 4100007

Hwasun-gun, Jeollanam-do, South Korea

Site Status

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, South Korea

Site Status

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, South Korea

Site Status

Investigational Site Number : 4100006

Incheon, , South Korea

Site Status

Investigational Site Number : 4100005

Seoul, , South Korea

Site Status

Investigational Site Number : 7240005

Santiago de Compostela, A Coruña [La Coruña], Spain

Site Status

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], Spain

Site Status

Investigational Site Number : 7240006

Santander, Cantabria, Spain

Site Status

Investigational Site Number : 7240002

Pamplona, Navarre, Spain

Site Status

Investigational Site Number : 7240003

Madrid, , Spain

Site Status

Investigational Site Number : 7240004

Salamanca, , Spain

Site Status

Investigational Site Number : 7520004

Luleå, , Sweden

Site Status

Investigational Site Number : 7520005

Uddevalla, , Sweden

Site Status

Investigational Site Number : 1580004

Kaohsiung City, , Taiwan

Site Status

Investigational Site Number : 1580002

Taichung, , Taiwan

Site Status

Investigational Site Number : 1580001

Taipei, , Taiwan

Site Status

Investigational Site Number : 1580003

Taoyuan District, , Taiwan

Site Status

Investigational Site Number : 7920001

Ankara, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920002

Antalya, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920005

Istanbul, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920006

Istanbul, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920003

Istanbul, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920004

Istanbul, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920008

Izmir, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920010

Izmir, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920009

Kayseri, , Turkey (Türkiye)

Site Status

Investigational Site Number : 7920007

Kocaeli, , Turkey (Türkiye)

Site Status

Investigational Site Number : 8260002

London, London, City of, United Kingdom

Site Status

Investigational Site Number : 8260003

London, London, City of, United Kingdom

Site Status

Investigational Site Number : 8260001

London, London, City of, United Kingdom

Site Status

Countries

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United States Australia Belgium Canada Czechia Denmark France Germany Greece Hungary Italy Japan New Zealand Norway Poland Portugal Russia Slovakia South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 36108425 (View on PubMed)

Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Mace S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. doi: 10.1016/S0140-6736(19)32556-5. Epub 2019 Nov 14.

Reference Type BACKGROUND
PMID: 31735560 (View on PubMed)

Richardson PG, Perrot A, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Malinge L, Dubin F, van de Velde H, Anderson KC. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022 Mar;23(3):416-427. doi: 10.1016/S1470-2045(22)00019-5. Epub 2022 Feb 10.

Reference Type BACKGROUND
PMID: 35151415 (View on PubMed)

Richardson PG, Perrot A, Miguel JS, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang SY, Minarik J, Cavo M, Prince HM, Mace S, Zhang R, Dubin F, Morisse MC, Anderson KC. Isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone in patients with relapsed and refractory multiple myeloma: final overall survival analysis. Haematologica. 2024 Jul 1;109(7):2239-2249. doi: 10.3324/haematol.2023.284325.

Reference Type DERIVED
PMID: 38299578 (View on PubMed)

Sunami K, Ikeda T, Huang SY, Wang MC, Koh Y, Min CK, Yeh SP, Matsumoto M, Uchiyama M, Iyama S, Shimazaki C, Lee JH, Kim K, Kaneko H, Kim JS, Lin TL, Campana F, Tada K, Iida S, Suzuki K; ICARIA-MM study group. Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):e751-e761. doi: 10.1016/j.clml.2022.04.005. Epub 2022 Apr 8.

Reference Type DERIVED
PMID: 35641409 (View on PubMed)

Wilmoth J, Colson K, Dubin F, Kellam C. Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. Clin J Oncol Nurs. 2021 Dec 1;25(6):706-712. doi: 10.1188/21.CJON.706-712.

Reference Type DERIVED
PMID: 34800109 (View on PubMed)

Bringhen S, Pour L, Vorobyev V, Vural F, Warzocha K, Benboubker L, Koh Y, Maisnar V, Karlin L, Pavic M, Campana F, Le Guennec S, Menas F, van de Velde H, Richardson PG. Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis. Leuk Res. 2021 May;104:106576. doi: 10.1016/j.leukres.2021.106576. Epub 2021 Mar 29.

Reference Type DERIVED
PMID: 33839618 (View on PubMed)

Schjesvold FH, Richardson PG, Facon T, Alegre A, Spencer A, Jurczyszyn A, Sunami K, Frenzel L, Min CK, Guillonneau S, Lin PL, Le-Guennec S, Campana F, van de Velde H, Bensfia S, Bringhen S. Isatuximab plus pomalidomide and dexamethasone in elderly patients with relapsed/refractory multiple myeloma: ICARIA-MM subgroup analysis. Haematologica. 2021 Apr 1;106(4):1182-1187. doi: 10.3324/haematol.2020.253450. No abstract available.

Reference Type DERIVED
PMID: 32586908 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U1111-1180-6262

Identifier Type: REGISTRY

Identifier Source: secondary_id

2016-003097-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC14335

Identifier Type: -

Identifier Source: org_study_id

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