Plasma Cell MyelomaPhase 3NCT04270409
Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma
A Phase 3 study testing Isatuximab SAR650984, Lenalidomide and Dexamethasone in people with Plasma Cell Myeloma, run by Sanofi at 105 sites in 24 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Plasma Cell Myeloma
- What is being tested?
- Isatuximab SAR650984, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 337 participants
- Where
- 105 sitesin 24 countries
- Study dates
- 16 Jun 2020to 21 Oct 2033
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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%
Show all 28Show fewer
- 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.
- Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met.
- Active hepatitis C virus (HCV) infection: positive HCV ribonucleic acid (RNA) and negative anti-HCV
- Of note:
- Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.
- Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible
- Malabsorption syndrome or any condition that can significantly impact the absorption of lenalidomide
- Any of the following within 3 months prior to randomization (or first study intervention administration in safety run-in cohort): treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event
- Received treatment (eg surgery, radiotherapy, medication) for a malignancy within 3 years of randomization (or first study intervention administration in safety run-in cohort)
- Prior exposure to approved or investigational treatments for SMM or multiple myeloma (MM) (including but not limited to conventional chemotherapies, immunomodulatory imid drugs, or Proteasome inhibitors); concurrent use of bisphosphonates or receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab is not permitted; however, prior bisphosphonates or once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is permitted
- Ongoing treatment with corticosteroids with a dose >10 mg prednisone or equivalent per day at the time of randomization (or first study intervention administration in safety run-in cohort)
- Women of childbearing potential or male participant with women of childbearing potential who do not agree to use a highly effective method of birth control
- Vaccination with a live vaccine 4 weeks before the start of the study drug. Seasonal flu vaccines that do not contain live virus are permitted
- The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Trial locations and contacts
105 sites in 24 countries.
105 sites in 24 countries
United States9 sites
Dana Farber Cancer Institute Site Number : 8400001
Boston, Massachusetts, 02115
Presbyterian Hospital Site Number : 8400015
Charlotte, North Carolina, 28204
Colorado Blood Cancer Institute Site Number : 8400007
Denver, Colorado, 80218
~University of Texas - MD Anderson Cancer Center Site Number : 8400002
Houston, Texas, 77030
Cancer Specialist of North Florida Site Number : 8400011
Jacksonville, Florida, 32256
UCLA Site Number : 8400010
Los Angeles, California, 90024
University of Miami Site Number : 8400012
Miami, Florida, 33136
Tennessee Oncology Site Number : 8400006
Nashville, Tennessee, 37203
Novant Health Forsyth Medical Center Site Number : 8401015
Winston-Salem, North Carolina, 27103
France9 sites
Investigational Site Number :2500009
Ars-Laquenexy, 57085
Investigational Site Number :2500010
Bayonne, 64109
Investigational Site Number :2500007
Grenoble, 38043
Investigational Site Number :2500006
La Roche-sur-Yon, 85925
Investigational Site Number :2500003
Lille, 59037
Investigational Site Number :2500005
Paris, 75012
Investigational Site Number :2500011
Paris, 75013
Investigational Site Number :2500002
Poitiers, 86021
Investigational Site Number :2500001
Rennes, 35033
Australia7 sites
Investigational Site Number :0360002
Fitzroy, Victoria, 3065
Investigational Site Number :0360007
Heidelberg West, Victoria, 3081
Investigational Site Number :0360008
Liverpool, New South Wales, 2170
Investigational Site Number :0360006
Nedlands, Western Australia, 6009
Investigational Site Number :0360004
Richmond, Victoria, 3121
Investigational Site Number :0360005
Waratah, New South Wales, 2298
Investigational Site Number :0360001
Wollongong, New South Wales, 2500
Japan7 sites
Investigational Site Number :3920005
Higashiibaraki-gun, Ibaraki, 311-3193
Investigational Site Number :3920006
Kamogawa-shi, Chiba, 296-8602
Investigational Site Number :3920008
Maebashi, Gunma, 371-8511
Investigational Site Number :3920002
Nagoya, Aichi-ken, 467-8602
Investigational Site Number :3920003
Okayama, Okayama-ken, 701-1192
Investigational Site Number :3920001
Shibuya-ku, Tokyo, 150-8935
Investigational Site Number :3920009
Sunto-gun, Shizuoka, 411-8777
Spain7 sites
Investigational Site Number :7240004
Barcelona, Barcelona [Barcelona], 08036
Investigational Site Number :7240001
Barcelona, Barcelona [Barcelona], 08041
Investigational Site Number :7240005
Madrid, 28041
Investigational Site Number :7240006
Pamplona, Navarre, 31008
Investigational Site Number :7240007
Salamanca, 37007
Investigational Site Number :7240002
Valencia, Valenciana, Comunidad, 46017
Investigational Site Number :7240003
Zaragoza, 50009
China6 sites
Investigational Site Number :1560002
Hangzhou, 310003
Investigational Site Number :1560003
Hangzhou, 310003
Investigational Site Number :1560006
Nanchang, 330006
Investigational Site Number :1560004
Shanghai, 200032
Investigational Site Number :1560005
Shenyang, 110022
Investigational Site Number :1560001
Tianjin, 300020
Israel6 sites
Investigational Site Number :3760004
Ashdod, 7747629
Investigational Site Number :3760001
Jerusalem, 91031
Investigational Site Number :3760002
Jerusalem, 91120
Investigational Site Number :3760005
Petah Tikva, 49100
Investigational Site Number :3760006
Ramat Gan, 5265601
Investigational Site Number :3760003
Tel Aviv, 64239
Czechia5 sites
Investigational Site Number : 2030004
Brno, 62500
Investigational Site Number : 2030005
Hradec Králové, 50005
Investigational Site Number : 2030002
Olomouc, 77900
Investigational Site Number : 2030003
Ostrava - Poruba, 70852
Investigational Site Number : 2030001
Prague, 12808
Italy5 sites
Investigational Site Number :3800005
Ancona, 60032
Investigational Site Number :3800003
Bologna, 40138
Investigational Site Number :3800006
Meldola, Forlì-Cesena, 47014
Investigational Site Number :3800001
Rozzano, Milano, 20089
Investigational Site Number :3800002
Terni, 05100
Turkey (Türkiye)5 sites
Investigational Site Number : 7920005
Ankara, 06010
Investigational Site Number : 7920001
Ankara, 06620
Investigational Site Number : 7920004
Istanbul, 34214
Investigational Site Number : 7920002
Istanbul, 34390
Investigational Site Number : 7920003
Izmir, 35040
Denmark4 sites
Investigational Site Number :2080001
Aalborg, 9000
Investigational Site Number :2080003
Aarhus N, 8200
Investigational Site Number :2080005
Copenhagen, 2100
Investigational Site Number :2080002
Roskilde, 4000
Hungary4 sites
Investigational Site Number :3480003
Budapest, 1083
Investigational Site Number :3480001
Budapest, 1097
Investigational Site Number :3480002
Debrecen, 4032
Investigational Site Number :3480004
Kaposvár, 7400
Poland4 sites
Investigational Site Number :6160006
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168
Investigational Site Number :6160005
Chorzów, Silesian Voivodeship, 41-500
Investigational Site Number :6160008
Gdansk, Pomeranian Voivodeship, 80-214
Investigational Site Number :6160002
Lodz, Lódzkie, 93-510
South Korea4 sites
Investigational Site Number :4100004
Gangnam-gu, Seoul-teukbyeolsi, 06351
Investigational Site Number :4100003
Seoul, Seoul-teukbyeolsi, 03080
Investigational Site Number :4100001
Seoul, Seoul-teukbyeolsi, 03722
Investigational Site Number :4100002
Seoul, 06591
United Kingdom4 sites
Investigational Site Number :8260002
Bournemouth, Hampshire, BH7 7DW
Investigational Site Number :8260001
Leicester, LE15WW
Investigational Site Number :8260003
London, London, City of, SE1 7EH
Investigational Site Number :8260004
Southampton, SO16 6YD
Canada3 sites
Investigational Site Number :1240004
Edmonton, Alberta, T6G 1Z2
Investigational Site Number :1240005
Moncton, New Brunswick, E1C 6Z8
Investigational Site Number :1240001
Montreal, Quebec, H1T 2M4
Greece3 sites
Investigational Site Number :3000002
Athens, 10676
Investigational Site Number :3000001
Athens, 11528
Investigational Site Number :3000003
Thessaloniki, PC 54007
Ireland3 sites
Investigational Site Number :3720001
Dublin, Dublin
Investigational Site Number :3720002
Dublin, Dublin
Investigational Site Number :3720003
Dublin, Dublin
Germany2 sites
Investigational Site Number :2760001
Hamburg, 20246
Investigational Site Number :2760002
Heidelberg, 69120
New Zealand2 sites
Investigational Site Number :5540004
Christchurch, Canterbury
Investigational Site Number :5540001
Hamilton, Waikato Region, 3204
Norway2 sites
Investigational Site Number :5780002
Bergen, 5021
Investigational Site Number :5780001
Oslo, 0450
Sweden2 sites
Investigational Site Number :7520001
Gothenburg, 413 45
Investigational Site Number :7520003
Helsingborg, 251 87
Brazil1 site
Investigational Site Number :0760002
São Paulo, São Paulo, 04537-081
About this study
Official title: 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
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
Read more
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)
Read the detailed description
Study duration is expected to be approximately 12 years, including a 42-day screening period, followed by an up to 36-month treatment period, and a follow-up period of approximately 9 years.
- Conditions
- Plasma Cell Myeloma
- Being tested
- Isatuximab SAR650984, Lenalidomide, Dexamethasone, Montelukast or equivalent, Acetaminophen
- Keywords
- Anti-CD38 monoclonal antibody
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isatuximab SAR650984Drug
Also called Sarclisa
Pharmaceutical for: Solution for infusion Route of administration: Intravenous
LenalidomideDrug
Pharmaceutical form: Capsules Route of administration: Oral
DexamethasoneDrug
Pharmaceutical form: Tablets and solution for injection Route of administration: Oral and intravenous
Montelukast or equivalentDrug
Auxiliary Medicinal Product (AxMP)/pre-medication; ATC code: R03DC03; Pharmaceutical form: tablet; Route of administration: Oral;
AcetaminophenDrug
AxMP/pre-medication ATC code: N02BE01 Pharmaceutical form: tablet/ampule/capsule; Route of administration: Intravenous (IV) or per os (PO)
Diphenhydramine or equivalentDrug
AxMP/pre-medication ATC code: R06AA02 Pharmaceutical form: ampule; Route of administration: Intravenous
Methylprednisolone or equivalentDrug
AxMP/pre-medication; ATC code: H02AB04; Pharmaceutical form: vial; Route of administration: Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Isatuximab, lenalidomide, and dexamethasone (ILd) | Experimental | Participants 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. Receives: Drug: Isatuximab SAR650984; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Montelukast or equivalent; Drug: Acetaminophen; Drug: Diphenhydramine or equivalent; Drug: Methylprednisolone or equivalent |
| Lenalidomide and dexamethasone (Ld) | Active comparator | Lenalidomide [PO administration] in combination with dexamethasone [PO administration] for 24 cycles. 1 cycle = 28 days Receives: Drug: Lenalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events- Safety Run-in Part
Measured: Up to approximately 63 months
Plasma concentration of isatuximab during the treatment period - Safety Run-in Part
Measured: 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
Measured: 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
Measured: Up to approximately 114 months
Secondary outcomes (29)
Overall Response Rate (ORR)- Safety Run-in Part
ORR defined as the proportion of participants with best overall response (BOR) recorded as partial response (PR) or better according to 2016 IMWG criteria
Measured: Up to approximately 63 months
Duration of Response (DOR) - Safety Run-in Part
DOR defined as the time from the date of the first response to date of first progressive disease (PD) or death, whichever happens first.
Measured: Up to approximately 63 months
Minimal residual disease (MRD) negativity -Safety Run-in Part
MRD negativity defined as the proportion of participants for whom MRD is negative in participants achieving very good partial response (VGPR) or above.
Measured: Up to approximately 36 months
Time to diagnostic (SLiM CRAB) progression or death - Safety Run-in Part
Time to diagnostic (SLiM CRAB) progression or death defined as the time from the date of the first study intervention administration to diagnosis of SLiM CRAB or other related conditions progression or death from any cause, whichever happens first.
Measured: Up to approximately 63 months
Time to first-line treatment for multiple myeloma (MM) - Safety Run-in Part
Time to first-line treatment for MM defined as the time from the date of the first study intervention administration to first-line treatment for MM.
Measured: Up to approximately 63 months
Number of participants with anti-drug antibodies (ADA) against isatuximab- Safety Run-in Part
Measured: Up to approximately 63 months
PFS in participants with chromosomal abnormalities - Safety Run-In Part
Association of chromosomal abnormalities with survival outcomes
Measured: Up to approximately 63 months
Overall Survival (OS) in participants with chromosomal abnormalities - Safety Run-In Part
Association of chromosomal abnormalities with survival outcomes
Measured: Up to approximately 63 months
Minimal residual disease (MRD) negativity - Randomized Phase 3 Part
MRD negativity defined as the proportion Number of participants for whom MRD is negative in participants achieving VGPR or above.
Measured: Up to approximately 36 months
Sustained MRD negativity - Randomized Phase 3 Part
Sustained MRD negativity defined as the proportion of participants for whom MRD is negative during a minimum period of one year.
Measured: Up to approximately 36 months
Second PFS (PFS2) - Randomized Phase 3 Part
PFS2 defined as the time from the date of randomization to the date of first documentation of PD (as reported by the Investigator) after initiation of further treatment for MM or the date of death from any cause, whichever happens first
Measured: Up to approximately 144 months
OS - Randomized Phase 3 Part
OS defined as the time from date of randomization to death from any cause.
Measured: Up to approximately 114 months
Complete response (CR) rate - Randomized Phase 3 Part
Percentage of participants with a CR (or better [stringent CR (sCR)]) as defined by 2016 IMWG response criteria, assessed by an IRC based on central laboratory values.
Measured: Up to approximately 114 months
Overall Response Rate (ORR) - Randomized Phase 3 Part
ORR is defined as the proportion of participants with BOR recorded as PR or better according to the 2016 IMWG criteria, assessed by an IRC based on central laboratory values.
Measured: Up to approximately 114 months
Duration of response (DOR) - Randomized Phase 3 Part
DOR is defined as the time from the date of the first IRC determined response to the date of first IRC PD, or death, whichever happens first.
Measured: Up to approximately 114 months
Time to diagnostic (SLiM CRAB) progression - Randomized Phase 3 Part
Time to diagnostic (SLiM CRAB) progression defined as the time from randomization to the date of diagnosis of SLiM CRAB progression based on IRC assessment.
Measured: Up to approximately 114 months
Time to biochemical progression - Randomized Phase 3 Part
Time to biochemical progression defined as the time from randomization to the date of biochemical progression based on IRC assessment.
Measured: Up to approximately 114 months
Time to first-line treatment for MM- Randomized Phase 3 Part
Time to first-line treatment for MM defined as the time from randomization to first-line treatment for MM
Measured: Up to approximately 144 months
PFS in participants with chromosomal abnormalities - Randomized Phase 3 Part
Association of chromosomal abnormalities with survival outcomes.
Measured: Up to approximately 114 months
OS in participants with chromosomal abnormalities - Randomized Phase 3 Part
Association of chromosomal abnormalities with survival outcomes.
Measured: Up to approximately 144 months
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events - Randomized Phase 3 Part
Measured: Up to approximately 144 months
Plasma concentration of isatuximab (Ctrough)- Safety Run-in and Randomized Phase 3 Part
Ctrough defined as concentration observed just before treatment administration during repeated dosing after IV administration
Measured: Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Concentration observed at the end of intravenous infusion.(Ceoi)- Safety Run-in Part
Measured: Day 1 of Cycle 1 to 4
Number of participants with Incidence of anti-drug antibodies (ADA) against isatuximab- Randomized Phase 3 Part
Measured: Up to approximately 144 months
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 - Randomized Phase 3 Part
The EORTC Multiple Myeloma Module (QLQ-C30) will be used to assess cancer-specific health related quality of life (HRQL), disease and treatment related symptoms and impact of symptoms. Mean change from baseline scores will be assessed, with responses ranging from 1=not at all to 4=very much or 1=very poor to 7=excellent; higher scores represent a better level of physical functioning
Measured: Baseline to follow-up (up to approximately 114 months)
EORTC QLQ-MY20 - Randomized Phase 3 Part
The EORTC Multiple Myeloma Module (QLQ-MY20) will be used to measure myeloma-specific HRQL, disease and treatment related symptoms and impact of symptoms. Mean change from baseline in scores will be assessed using a 4-point scale, with responses ranging from 1=not at all to 4=very much; higher scores represent better perspectives of the future and higher level of symptomatology
Measured: Baseline to follow-up (up to approximately 114 months)
EQ-5D-5L - Randomized Phase 3 Part
The EQ-5D-5L will be used to assess health status and health utility. Mean change from baseline scores will be assessed from 5 items, with responses ranging from 'no' to 'extreme problems'; health state utility values (HSUVs) are generated by multiplying the item scores by country specific value sets; health status is assessed via a VAS; higher scores = higher HSUV/health status
Measured: Baseline to follow-up (up to approximately 114 months)
Randomized Phase 3: HRUPQ - Randomized Phase 3 Part
Mean change from baseline in Health resource utilization and productivity questionnaire (HRUPQ) scores. HRUPQ will assess health care resource utilization of HRSM and the impact of high risk smoldering multiple myeloma (HRSMM) on employment/work; higher scores = greater impact on work/productivity, resources.
Measured: Baseline to follow-up (up to approximately 114 months)
Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2) - Randomized Phase 3 Part
PQAT-v2 will be used to assess participant-perceived advantages and disadvantages of treatment. Patient's qualitative assessment of treatment will be assessed using a 10 point VAS/NRS scale with response anchors of 'not beneficial at all' to 'extremely beneficial'; higher scores represent greater patient-perceived benefits of treatment
Measured: End of treatment (up to approximately 3 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start16 Jun 2020
- Primary completion14 Oct 2030 (estimated)
- Study completion21 Oct 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 337 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04270409
- Sponsor's protocol ID
- EFC15992
- Other IDs
- U1111-1222-7068, 2023-507419-37, 2019-003139-47, 2019, 2023
- Status last verified
- Dec 2025
- First submitted
- 13 Feb 2020
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04270409
- Acronym / sponsor ID
- EFC15992
- Conditions
- Plasma Cell Myeloma
- Keywords
- Anti-CD38 monoclonal antibody
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 337 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 16 Jun 2020 (actual)
- Primary completion
- 14 Oct 2030 (estimated)
- Study completion
- 21 Oct 2033 (estimated)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
Study duration is expected to be approximately 12 years, including a 42-day screening period, followed by an up to 36-month treatment period, and a follow-up period of approximately 9 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isatuximab, lenalidomide, and dexamethasone (ILd) | Experimental | Drug: Isatuximab SAR650984, Drug: Lenalidomide, Drug: Dexamethasone, Drug: Montelukast or equivalent, Drug: Acetaminophen, Drug: Diphenhydramine or equivalent, Drug: Methylprednisolone or equivalentParticipants 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 comparator | Drug: Lenalidomide, Drug: DexamethasoneLenalidomide [PO administration] in combination with dexamethasone [PO administration] for 24 cycles. 1 cycle = 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (28 listed)
- 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):
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isatuximab SAR650984Also: SarclisaPharmaceutical for: Solution for infusion Route of administration: Intravenous | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd) |
| LenalidomidePharmaceutical form: Capsules Route of administration: Oral | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd), Lenalidomide and dexamethasone (Ld) |
| DexamethasonePharmaceutical form: Tablets and solution for injection Route of administration: Oral and intravenous | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd), Lenalidomide and dexamethasone (Ld) |
| Montelukast or equivalentAuxiliary Medicinal Product (AxMP)/pre-medication; ATC code: R03DC03; Pharmaceutical form: tablet; Route of administration: Oral; | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd) |
| AcetaminophenAxMP/pre-medication ATC code: N02BE01 Pharmaceutical form: tablet/ampule/capsule; Route of administration: Intravenous (IV) or per os (PO) | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd) |
| Diphenhydramine or equivalentAxMP/pre-medication ATC code: R06AA02 Pharmaceutical form: ampule; Route of administration: Intravenous | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd) |
| Methylprednisolone or equivalentAxMP/pre-medication; ATC code: H02AB04; Pharmaceutical form: vial; Route of administration: Intravenous | Drug | Isatuximab, lenalidomide, and dexamethasone (ILd) |
Primary outcome
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events- Safety Run-in Part
Time frame: Up to approximately 63 months
Plasma concentration of isatuximab during the treatment period - Safety Run-in Part
Time frame: After first infusion from Cycle 1 Day 1 to Day 28 in safety run-in part
Receptor density/receptor occupancy Safety Run-in Part
Time frame: Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Change in CD38 receptor occupancy from baseline
Progression-free survival (PFS) Randomized Phase 3 Part
Time frame: Up to approximately 114 months
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
29 secondary outcomes
Overall Response Rate (ORR)- Safety Run-in Part
Time frame: Up to approximately 63 months
Duration of Response (DOR) - Safety Run-in Part
Time frame: Up to approximately 63 months
Minimal residual disease (MRD) negativity -Safety Run-in Part
Time frame: Up to approximately 36 months
Time to diagnostic (SLiM CRAB) progression or death - Safety Run-in Part
Time frame: Up to approximately 63 months
Time to first-line treatment for multiple myeloma (MM) - Safety Run-in Part
Time frame: Up to approximately 63 months
Number of participants with anti-drug antibodies (ADA) against isatuximab- Safety Run-in Part
Time frame: Up to approximately 63 months
PFS in participants with chromosomal abnormalities - Safety Run-In Part
Time frame: Up to approximately 63 months
Overall Survival (OS) in participants with chromosomal abnormalities - Safety Run-In Part
Time frame: Up to approximately 63 months
Minimal residual disease (MRD) negativity - Randomized Phase 3 Part
Time frame: Up to approximately 36 months
Sustained MRD negativity - Randomized Phase 3 Part
Time frame: Up to approximately 36 months
Second PFS (PFS2) - Randomized Phase 3 Part
Time frame: Up to approximately 144 months
OS - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
Complete response (CR) rate - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
Overall Response Rate (ORR) - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
Duration of response (DOR) - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
Time to diagnostic (SLiM CRAB) progression - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
Time to biochemical progression - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
Time to first-line treatment for MM- Randomized Phase 3 Part
Time frame: Up to approximately 144 months
PFS in participants with chromosomal abnormalities - Randomized Phase 3 Part
Time frame: Up to approximately 114 months
OS in participants with chromosomal abnormalities - Randomized Phase 3 Part
Time frame: Up to approximately 144 months
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events - Randomized Phase 3 Part
Time frame: Up to approximately 144 months
Plasma concentration of isatuximab (Ctrough)- Safety Run-in and Randomized Phase 3 Part
Time frame: Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Concentration observed at the end of intravenous infusion.(Ceoi)- Safety Run-in Part
Time frame: Day 1 of Cycle 1 to 4
Number of participants with Incidence of anti-drug antibodies (ADA) against isatuximab- Randomized Phase 3 Part
Time frame: Up to approximately 144 months
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 - Randomized Phase 3 Part
Time frame: Baseline to follow-up (up to approximately 114 months)
EORTC QLQ-MY20 - Randomized Phase 3 Part
Time frame: Baseline to follow-up (up to approximately 114 months)
EQ-5D-5L - Randomized Phase 3 Part
Time frame: Baseline to follow-up (up to approximately 114 months)
Randomized Phase 3: HRUPQ - Randomized Phase 3 Part
Time frame: Baseline to follow-up (up to approximately 114 months)
Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2) - Randomized Phase 3 Part
Time frame: End of treatment (up to approximately 3 year)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- EFC15992 Plain Language Results SummariesLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
105 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Isatuximab SAR650984, Lenalidomide and Dexamethasone in people with Plasma Cell Myeloma, run by Sanofi at 105 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 105 sites in United States, France, Australia, Japan, Spain and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events- Safety Run-in Part (time frame: Up to approximately 63 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.