Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma
A Phase 3 Randomized, Open-label, Multicenter Study of Isatuximab (SAR650984) in Combination With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With High-risk Smoldering Multiple Myeloma
4 other identifiers
interventional
337
24 countries
105
Brief Summary
Primary Objectives:
- Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM)
- Randomized Phase 3 Part: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression-free survival when compared to lenalidomide and dexamethasone in subjects with high-risk SMM Secondary Objectives: Safety run-in Part:
- To assess overall response rate (ORR)
- To assess duration of response (DOR)
- To assess minimal residual disease (MRD) negativity in participants achieving very good partial response (VGPR) or complete response (CR)
- To assess time to diagnostic (SLiM CRAB) progression or death
- To assess time to first-line treatment for multiple myeloma (MM)
- To assess the potential immunogenicity of isatuximab
- Impact of abnormal chromosomal subtype on participant outcome Randomized Phase 3 Part: Key Secondary Objectives: To compare between the arms
- MRD negativity
- Sustained MRD negativity
- Second progression-free survival (PFS2)
- Overall survival Other Secondary Objectives: To evaluate in both arms
- CR rate
- ORR
- DOR
- Time to diagnostic (SLiM CRAB) progression
- Time to biochemical progression
- Time to first-line treatment for MM
- Impact of abnormal chromosomal subtype on participant outcome
- Safety and tolerability
- Pharmacokinetics (PK)
- Potential of isatuximab immunogenicity
- Clinical outcome assessments (COAs)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2020
Longer than P75 for phase_3
105 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 13, 2020
CompletedFirst Posted
Study publicly available on registry
February 17, 2020
CompletedStudy Start
First participant enrolled
June 16, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 14, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 21, 2033
December 12, 2025
December 1, 2025
10.3 years
February 13, 2020
December 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events- Safety Run-in Part
Up to approximately 63 months
Plasma concentration of isatuximab during the treatment period - Safety Run-in Part
After first infusion from Cycle 1 Day 1 to Day 28 in safety run-in part
Receptor density/receptor occupancy Safety Run-in Part
Change in CD38 receptor occupancy from baseline
Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Progression-free survival (PFS) Randomized Phase 3 Part
PFS defined as the time from randomization to MM (SLiM CRAB criteria) or other related conditions based on independent review committee (IRC) assessment according to 2014 International Myeloma Working Group (IMWG) criteria or death from any cause, whichever happens first
Up to approximately 114 months
Secondary Outcomes (29)
Overall Response Rate (ORR)- Safety Run-in Part
Up to approximately 63 months
Duration of Response (DOR) - Safety Run-in Part
Up to approximately 63 months
Minimal residual disease (MRD) negativity -Safety Run-in Part
Up to approximately 36 months
Time to diagnostic (SLiM CRAB) progression or death - Safety Run-in Part
Up to approximately 63 months
Time to first-line treatment for multiple myeloma (MM) - Safety Run-in Part
Up to approximately 63 months
- +24 more secondary outcomes
Study Arms (2)
Isatuximab, lenalidomide, and dexamethasone (ILd)
EXPERIMENTALParticipants will receive isatuximab \[intravenous (IV) administration\] in combination with lenalidomide \[per os (PO) administration\] and dexamethasone \[IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles\] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
Lenalidomide and dexamethasone (Ld)
ACTIVE COMPARATORLenalidomide \[PO administration\] in combination with dexamethasone \[PO administration\] for 24 cycles. 1 cycle = 28 days
Interventions
Pharmaceutical form: Capsules Route of administration: Oral
Pharmaceutical for: Solution for infusion Route of administration: Intravenous
Pharmaceutical form: Tablets and solution for injection Route of administration: Oral and intravenous
Auxiliary Medicinal Product (AxMP)/pre-medication; ATC code: R03DC03; Pharmaceutical form: tablet; Route of administration: Oral;
AxMP/pre-medication ATC code: N02BE01 Pharmaceutical form: tablet/ampule/capsule; Route of administration: Intravenous (IV) or per os (PO)
AxMP/pre-medication ATC code: R06AA02 Pharmaceutical form: ampule; Route of administration: Intravenous
AxMP/pre-medication; ATC code: H02AB04; Pharmaceutical form: vial; Route of administration: Intravenous
Eligibility Criteria
You may qualify if:
- Participants who are diagnosed within 5 years with SMM (per International Myeloma Working Group \[IMWG\] criteria), defined as serum M-protein ≥30 g/L or urinary M-protein ≥500 mg per 24 hour or both, and/or clonal bone marrow plasma cells (BMPCs) 10% to \<60%, and absence of myeloma defining events or other related conditions and with high-risk SMM
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or 2
- Capable of giving voluntary written informed consent
- Absolute neutrophil count (ANC) ≥1000/µL (1 × 10\^9/L)
- Platelets ≥50,000/µL (50 × 10\^9/L)
- Total bilirubin ≤3 mg/dL (except Gilbert syndrome, in which direct bilirubin should be -≤5 mg/dL).
- Alanine aminotransferase ≤3× upper limit of normal (ULN), aspartate aminotransferase ≤ 3 × ULN.
You may not qualify if:
- Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement):
- Increased calcium levels: Corrected serum calcium \>1 mg/dL above the ULN or \>11 mg/dL
- Renal insufficiency: Determined by glomerular filtration rate (GFR) \<40 mL/min/1.73 m² (Modification of Diet in Renal Disease \[MDRD\] Formula) or serum creatinine \>2 mg/dL
- Anemia (hemoglobin 2 g/dL below lower limit of normal or \<10 g/dL or both) transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
- ≥ 1 bone lytic lesion
- BMPCs ≥60%
- Serum involved/uninvolved FLC ratio ≥100 and an involved FLC ≥100mg/L
- Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 bone focal lesion (≥5 mm in diameter by MRI)
- Primary systemic amyloid light-chain (AL) amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, soft tissue plasmacytoma, symptomatic myeloma
- Uncontrolled infection within 28 days prior to randomization in Phase 3 or first study intervention administration in safety run-in
- Clinically significant cardiac or vascular disease within 3 months prior to randomization, e.g. Myocardial Infarction; Unstable Angina; Coronary (e.g. Coronary Artery Bypass Graft, Percutaneous Coronary Intervention) or peripheral artery revascularization, Left Ventricular Ejection Fraction \<40%, Heart Failure NYHA III-IV, Stroke, Transient Ischemic Attack, Pulmonary Embolism, other thromboembolic event, cardiac arrhythmia (Grade 3 or higher by NCI-CTCAE Version 5.0)
- Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A (defined as positive hepatitis A antigen or positive IgM). HIV serology at screening will be tested for German participants and any other country where required as per local regulations and serology hepatitis B and C at screening will be tested for all participants
- Uncontrolled or active hepatitis B virus (HBV) infection: Patients with positive Hepatitis B surface antigen (HBsAg) and/or HBV Deoxyribonucleic acid (DNA)
- Of note:
- Patient can be eligible if anti-HBc Immunoglobulin G (IgG) positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sanofilead
Study Sites (105)
UCLA Site Number : 8400010
Los Angeles, California, 90024, United States
Colorado Blood Cancer Institute Site Number : 8400007
Denver, Colorado, 80218, United States
Cancer Specialist of North Florida Site Number : 8400011
Jacksonville, Florida, 32256, United States
University of Miami Site Number : 8400012
Miami, Florida, 33136, United States
Dana Farber Cancer Institute Site Number : 8400001
Boston, Massachusetts, 02115, United States
Presbyterian Hospital Site Number : 8400015
Charlotte, North Carolina, 28204, United States
Novant Health Forsyth Medical Center Site Number : 8401015
Winston-Salem, North Carolina, 27103, United States
Tennessee Oncology Site Number : 8400006
Nashville, Tennessee, 37203, United States
~University of Texas - MD Anderson Cancer Center Site Number : 8400002
Houston, Texas, 77030, United States
Investigational Site Number :0360008
Liverpool, New South Wales, 2170, Australia
Investigational Site Number :0360005
Waratah, New South Wales, 2298, Australia
Investigational Site Number :0360001
Wollongong, New South Wales, 2500, Australia
Investigational Site Number :0360002
Fitzroy, Victoria, 3065, Australia
Investigational Site Number :0360007
Heidelberg West, Victoria, 3081, Australia
Investigational Site Number :0360004
Richmond, Victoria, 3121, Australia
Investigational Site Number :0360006
Nedlands, Western Australia, 6009, Australia
Investigational Site Number :0760002
São Paulo, São Paulo, 04537-081, Brazil
Investigational Site Number :1240004
Edmonton, Alberta, T6G 1Z2, Canada
Investigational Site Number :1240005
Moncton, New Brunswick, E1C 6Z8, Canada
Investigational Site Number :1240001
Montreal, Quebec, H1T 2M4, Canada
Investigational Site Number :1560002
Hangzhou, 310003, China
Investigational Site Number :1560003
Hangzhou, 310003, China
Investigational Site Number :1560006
Nanchang, 330006, China
Investigational Site Number :1560004
Shanghai, 200032, China
Investigational Site Number :1560005
Shenyang, 110022, China
Investigational Site Number :1560001
Tianjin, 300020, China
Investigational Site Number : 2030004
Brno, 62500, Czechia
Investigational Site Number : 2030005
Hradec Králové, 50005, Czechia
Investigational Site Number : 2030002
Olomouc, 77900, Czechia
Investigational Site Number : 2030003
Ostrava - Poruba, 70852, Czechia
Investigational Site Number : 2030001
Prague, 12808, Czechia
Investigational Site Number :2080001
Aalborg, 9000, Denmark
Investigational Site Number :2080003
Aarhus N, 8200, Denmark
Investigational Site Number :2080005
Copenhagen, 2100, Denmark
Investigational Site Number :2080002
Roskilde, 4000, Denmark
Investigational Site Number :2500009
Ars-Laquenexy, 57085, France
Investigational Site Number :2500010
Bayonne, 64109, France
Investigational Site Number :2500007
Grenoble, 38043, France
Investigational Site Number :2500006
La Roche-sur-Yon, 85925, France
Investigational Site Number :2500003
Lille, 59037, France
Investigational Site Number :2500005
Paris, 75012, France
Investigational Site Number :2500011
Paris, 75013, France
Investigational Site Number :2500002
Poitiers, 86021, France
Investigational Site Number :2500001
Rennes, 35033, France
Investigational Site Number :2760001
Hamburg, 20246, Germany
Investigational Site Number :2760002
Heidelberg, 69120, Germany
Investigational Site Number :3000002
Athens, 10676, Greece
Investigational Site Number :3000001
Athens, 11528, Greece
Investigational Site Number :3000003
Thessaloniki, PC 54007, Greece
Investigational Site Number :3480003
Budapest, 1083, Hungary
Investigational Site Number :3480001
Budapest, 1097, Hungary
Investigational Site Number :3480002
Debrecen, 4032, Hungary
Investigational Site Number :3480004
Kaposvár, 7400, Hungary
Investigational Site Number :3720001
Dublin, Dublin, Ireland
Investigational Site Number :3720002
Dublin, Dublin, Ireland
Investigational Site Number :3720003
Dublin, Dublin, Ireland
Investigational Site Number :3760004
Ashdod, 7747629, Israel
Investigational Site Number :3760001
Jerusalem, 91031, Israel
Investigational Site Number :3760002
Jerusalem, 91120, Israel
Investigational Site Number :3760005
Petah Tikva, 49100, Israel
Investigational Site Number :3760006
Ramat Gan, 5265601, Israel
Investigational Site Number :3760003
Tel Aviv, 64239, Israel
Investigational Site Number :3800006
Meldola, Forlì-Cesena, 47014, Italy
Investigational Site Number :3800001
Rozzano, Milano, 20089, Italy
Investigational Site Number :3800005
Ancona, 60032, Italy
Investigational Site Number :3800003
Bologna, 40138, Italy
Investigational Site Number :3800002
Terni, 05100, Italy
Investigational Site Number :3920002
Nagoya, Aichi-ken, 467-8602, Japan
Investigational Site Number :3920006
Kamogawa-shi, Chiba, 296-8602, Japan
Investigational Site Number :3920008
Maebashi, Gunma, 371-8511, Japan
Investigational Site Number :3920005
Higashiibaraki-gun, Ibaraki, 311-3193, Japan
Investigational Site Number :3920003
Okayama, Okayama-ken, 701-1192, Japan
Investigational Site Number :3920009
Sunto-gun, Shizuoka, 411-8777, Japan
Investigational Site Number :3920001
Shibuya-ku, Tokyo, 150-8935, Japan
Investigational Site Number :4400001
Vilnius, 08661, Lithuania
Investigational Site Number :5540004
Christchurch, Canterbury, New Zealand
Investigational Site Number :5540001
Hamilton, Waikato Region, 3204, New Zealand
Investigational Site Number :5780002
Bergen, 5021, Norway
Investigational Site Number :5780001
Oslo, 0450, Norway
Investigational Site Number :6160006
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168, Poland
Investigational Site Number :6160002
Lodz, Lódzkie, 93-510, Poland
Investigational Site Number :6160008
Gdansk, Pomeranian Voivodeship, 80-214, Poland
Investigational Site Number :6160005
Chorzów, Silesian Voivodeship, 41-500, Poland
Investigational Site Number :4100004
Gangnam-gu, Seoul-teukbyeolsi, 06351, South Korea
Investigational Site Number :4100003
Seoul, Seoul-teukbyeolsi, 03080, South Korea
Investigational Site Number :4100001
Seoul, Seoul-teukbyeolsi, 03722, South Korea
Investigational Site Number :4100002
Seoul, 06591, South Korea
Investigational Site Number :7240004
Barcelona, Barcelona [Barcelona], 08036, Spain
Investigational Site Number :7240001
Barcelona, Barcelona [Barcelona], 08041, Spain
Investigational Site Number :7240006
Pamplona, Navarre, 31008, Spain
Investigational Site Number :7240002
Valencia, Valenciana, Comunidad, 46017, Spain
Investigational Site Number :7240005
Madrid, 28041, Spain
Investigational Site Number :7240007
Salamanca, 37007, Spain
Investigational Site Number :7240003
Zaragoza, 50009, Spain
Investigational Site Number :7520001
Gothenburg, 413 45, Sweden
Investigational Site Number :7520003
Helsingborg, 251 87, Sweden
Investigational Site Number : 7920005
Ankara, 06010, Turkey (Türkiye)
Investigational Site Number : 7920001
Ankara, 06620, Turkey (Türkiye)
Investigational Site Number : 7920004
Istanbul, 34214, Turkey (Türkiye)
Investigational Site Number : 7920002
Istanbul, 34390, Turkey (Türkiye)
Investigational Site Number : 7920003
Izmir, 35040, Turkey (Türkiye)
Investigational Site Number :8260002
Bournemouth, Hampshire, BH7 7DW, United Kingdom
Investigational Site Number :8260003
London, London, City of, SE1 7EH, United Kingdom
Investigational Site Number :8260001
Leicester, LE15WW, United Kingdom
Investigational Site Number :8260004
Southampton, SO16 6YD, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Sciences & Operations
Sanofi
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 13, 2020
First Posted
February 17, 2020
Study Start
June 16, 2020
Primary Completion (Estimated)
October 14, 2030
Study Completion (Estimated)
October 21, 2033
Last Updated
December 12, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org