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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 Purpose

Plasma Cell Myeloma

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Isatuximab SAR650984
Lenalidomide
Dexamethasone
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Plasma Cell Myeloma focused on measuring Anti-CD38 monoclonal antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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 (immunoglobulin light chain) 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 disease, including:

    • Myocardial infarction within 6 months with left ventricular dysfunction or uncontrolled ischemic cardiac disease before Cycle 1 Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV)
    • Uncontrolled cardiac arrhythmia (Grade 2 or higher by NCI-CTCAE Version 5.0) or clinically significant electrocardiogram (ECG) abnormalities
  • 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 HBV infection: Patients with positive HBsAg and/or HBV DNA

Of note:

Patient can be eligible if anti-HBc 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 HCV infection: positive HCV 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 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.

Sites / Locations

  • UCLA-Site Number:8400010Recruiting
  • Colorado Blood Cancer Institute-Site Number:8400007Recruiting
  • Cancer Specialist of North Florida-Site Number:8400011Recruiting
  • University of Miami-Site Number:8400012Recruiting
  • Dana Farber Cancer Institute-Site Number:8400001Recruiting
  • Presbyterian Hospital-Site Number:8400015Recruiting
  • Novant Health Forsyth Medical Center-Site Number:8401015Recruiting
  • Tennessee Oncology, PLLC-Site Number:8400006Recruiting
  • ~University of Texas - MD Anderson Cancer Center-Site Number:8400002Recruiting
  • Investigational Site Number :0360008
  • Investigational Site Number :0360005
  • Investigational Site Number :0360001
  • Investigational Site Number :0360002
  • Investigational Site Number :0360007
  • Investigational Site Number :0360004
  • Investigational Site Number :0360006
  • Investigational Site Number :0760002
  • Investigational Site Number :1240004
  • Investigational Site Number :1240005
  • Investigational Site Number :1240001
  • Investigational Site Number :1560002
  • Investigational Site Number :1560003
  • Investigational Site Number :1560006
  • Investigational Site Number :1560004
  • Investigational Site Number :1560005
  • Investigational Site Number :1560001
  • Investigational Site Number :2080001
  • Investigational Site Number :2080003
  • Investigational Site Number :2080005
  • Investigational Site Number :2080002
  • Investigational Site Number :2500009
  • Investigational Site Number :2500010
  • Investigational Site Number :2500007
  • Investigational Site Number :2500006
  • Investigational Site Number :2500003
  • Investigational Site Number :2500005
  • Investigational Site Number :2500011
  • Investigational Site Number :2500002
  • Investigational Site Number :2500001
  • Investigational Site Number :2760001
  • Investigational Site Number :2760002
  • Investigational Site Number :3000002
  • Investigational Site Number :3000001
  • Investigational Site Number :3000003
  • Investigational Site Number :3480003
  • Investigational Site Number :3480001
  • Investigational Site Number :3480002
  • Investigational Site Number :3480004
  • Investigational Site Number :3720003
  • Investigational Site Number :3720002
  • Investigational Site Number :3720001
  • Investigational Site Number :3760004
  • Investigational Site Number :3760001
  • Investigational Site Number :3760002
  • Investigational Site Number :3760005
  • Investigational Site Number :3760006
  • Investigational Site Number :3760003
  • Investigational Site Number :3800006
  • Investigational Site Number :3800001
  • Investigational Site Number :3800005
  • Investigational Site Number :3800003
  • Investigational Site Number :3800002
  • Investigational Site Number :3920002
  • Investigational Site Number :3920006
  • Investigational Site Number :3920008
  • Investigational Site Number :3920005
  • Investigational Site Number :3920003
  • Investigational Site Number :3920009
  • Investigational Site Number :3920001
  • Investigational Site Number :4100004
  • Investigational Site Number :4100003
  • Investigational Site Number :4100001
  • Investigational Site Number :4100002
  • Investigational Site Number :4400001
  • Investigational Site Number :5540004
  • Investigational Site Number :5540001
  • Investigational Site Number :5780002
  • Investigational Site Number :5780001
  • Investigational Site Number :6160006
  • Investigational Site Number :6160002
  • Investigational Site Number :6160008
  • Investigational Site Number :6160005
  • Investigational Site Number :7240004
  • Investigational Site Number :7240001
  • Investigational Site Number :7240006
  • Investigational Site Number :7240002
  • Investigational Site Number :7240005
  • Investigational Site Number :7240007
  • Investigational Site Number :7240003
  • Investigational Site Number :7520001
  • Investigational Site Number :7520003
  • Investigational Site Number :8260002
  • Investigational Site Number :8260003
  • Investigational Site Number :8260001
  • Investigational Site Number :8260004

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Isatuximab, lenalidomide, and dexamethasone (ILd)

Lenalidomide and dexamethasone (Ld)

Arm Description

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

Lenalidomide [PO administration] in combination with dexamethasone [PO administration] for 24 cycles. 1 cycle = 28 days

Outcomes

Primary Outcome Measures

Safety assessment: adverse events (AEs)- Safety Run-in Part
Number of participants with AEs
Plasma concentration of isatuximab: Cmax- Safety Run-in Part
Maximum concentration observed after the first infusion (Cmax)
Receptor density/receptor occupancy Safety Run-in Part
Change in CD38 receptor occupancy from baseline
Progression-free survival (PFS) Randomized Phase 3
Time from randomization to MM (SLiM CRAB criteria) or other related conditions based on independent review committee assessment according to 2014 International Myeloma Working Group (IMWG) criteria or death from any cause, whichever happens first

Secondary Outcome Measures

Overall response rate (ORR)- Safety Run-in Part and Randomized Phase 3
Proportion of participants with best overall response recorded as partial response or better according to 2016 IMWG criteria
Duration of response (DOR)-Safety Run-in Part and Randomized Phase 3
Time from the date of the first response to date of progressive disease or death, whichever happens first
Minimal residual disease (MRD) negativity-Safety Run-in Part and Randomized Phase 3
Number of participants for whom MRD is negative
Time to diagnostic (SLiM CRAB) progression or death -Safety Run-in Part and Randomized Phase 3
Time from randomization to diagnosis of SLiM-CRAB or other related conditions, progression, or death from any cause
Time to first-line treatment for multiple myeloma (MM)- Safety Run-in Part and Randomized Phase 3
Time from randomization to first-line treatment for MM
Immunogenicity: Incidence of anti-drug antibodies (ADA)- Safety Run-in Part
Number of participants with anti-drug antibodies against isatuximab
Sustained MRD negativity- Randomized Phase 3
Number of participants with sustained MRD negativity (sample is still negative at least 1 year after the first negativity assessment)
Second PFS (PFS2) Randomized Phase 3
Time from randomization to date of second objective progressive disease or death from any cause
Overall survival- Randomized Phase 3
Time from date of randomization to death from any cause
PFS and OS in participants with cytogenetic abnormalities- Safety Run-In and Randomized Part
Association of cytogenetic abnormalities with survival outcomes
Complete response rate - Randomized Phase 3
Percentage of particpants with a CR as defined by 2016 IMWG response criteria
Time to biochemical progression - Randomized Phase 3
Time to biochemical progression is defined as the time from randomization to the date of biochemical progression based on IRC assessment.
Safety assessment: adverse events (AEs)- Randomized Phase 3
Number of participants with AEs
Plasma concentration of isatuximab- Randomized Phase 3
Concentration observed just before treatment administration during repeated dosing (Ctrough) after IV administration
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30-Randomized Phase 3
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
EORTC QLQ-MY20 - Randomized Phase 3
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
EQ-5D-5L Randomized Phase 3
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
Randomized Phase 3: HRUPQ - Randomized Phase 3
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 HRSM on employment/work higher scores = greater impact on work/productivity, resources
Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2) Randomized Phase 3
Patient's qualitative assessment of treatment will be assessed using a 10 point visual analogue/numeric rating scale with response anchors of 'not beneficial at all' to 'extremely beneficial'; higher scores represent greater patient-perceived benefits of treatment

Full Information

First Posted
February 13, 2020
Last Updated
August 17, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT04270409
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 11, 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 16, 2020 (Actual)
Primary Completion Date
June 1, 2028 (Anticipated)
Study Completion Date
October 1, 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary Objectives: Safety run-in: 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: 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 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 cytogenetic subtype on participant outcome Randomized Phase 3 - 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasma Cell Myeloma
Keywords
Anti-CD38 monoclonal antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
320 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Isatuximab, lenalidomide, and dexamethasone (ILd)
Arm Type
Experimental
Arm Description
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
Arm Title
Lenalidomide and dexamethasone (Ld)
Arm Type
Active Comparator
Arm Description
Lenalidomide [PO administration] in combination with dexamethasone [PO administration] for 24 cycles. 1 cycle = 28 days
Intervention Type
Drug
Intervention Name(s)
Isatuximab SAR650984
Other Intervention Name(s)
Sarclisa
Intervention Description
Pharmaceutical for: Solution for infusion Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Pharmaceutical form: Capsules Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Pharmaceutical form: Tablets and solution for injection Route of administration: Oral and intravenous
Primary Outcome Measure Information:
Title
Safety assessment: adverse events (AEs)- Safety Run-in Part
Description
Number of participants with AEs
Time Frame
Up to approximately 63 months
Title
Plasma concentration of isatuximab: Cmax- Safety Run-in Part
Description
Maximum concentration observed after the first infusion (Cmax)
Time Frame
After first infusion in Cycle 1 in safety run-in part. 1 cycle = 28 days
Title
Receptor density/receptor occupancy Safety Run-in Part
Description
Change in CD38 receptor occupancy from baseline
Time Frame
Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Title
Progression-free survival (PFS) Randomized Phase 3
Description
Time from randomization to MM (SLiM CRAB criteria) or other related conditions based on independent review committee assessment according to 2014 International Myeloma Working Group (IMWG) criteria or death from any cause, whichever happens first
Time Frame
Up to approximately 114 months
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)- Safety Run-in Part and Randomized Phase 3
Description
Proportion of participants with best overall response recorded as partial response or better according to 2016 IMWG criteria
Time Frame
Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively
Title
Duration of response (DOR)-Safety Run-in Part and Randomized Phase 3
Description
Time from the date of the first response to date of progressive disease or death, whichever happens first
Time Frame
Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively
Title
Minimal residual disease (MRD) negativity-Safety Run-in Part and Randomized Phase 3
Description
Number of participants for whom MRD is negative
Time Frame
Up to approximately 65 months
Title
Time to diagnostic (SLiM CRAB) progression or death -Safety Run-in Part and Randomized Phase 3
Description
Time from randomization to diagnosis of SLiM-CRAB or other related conditions, progression, or death from any cause
Time Frame
Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively
Title
Time to first-line treatment for multiple myeloma (MM)- Safety Run-in Part and Randomized Phase 3
Description
Time from randomization to first-line treatment for MM
Time Frame
Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively
Title
Immunogenicity: Incidence of anti-drug antibodies (ADA)- Safety Run-in Part
Description
Number of participants with anti-drug antibodies against isatuximab
Time Frame
Up to approximately 27 months
Title
Sustained MRD negativity- Randomized Phase 3
Description
Number of participants with sustained MRD negativity (sample is still negative at least 1 year after the first negativity assessment)
Time Frame
Up to approximately 65 months
Title
Second PFS (PFS2) Randomized Phase 3
Description
Time from randomization to date of second objective progressive disease or death from any cause
Time Frame
Up to approximately 144 months
Title
Overall survival- Randomized Phase 3
Description
Time from date of randomization to death from any cause
Time Frame
Up to approximately 144 months
Title
PFS and OS in participants with cytogenetic abnormalities- Safety Run-In and Randomized Part
Description
Association of cytogenetic abnormalities with survival outcomes
Time Frame
Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively
Title
Complete response rate - Randomized Phase 3
Description
Percentage of particpants with a CR as defined by 2016 IMWG response criteria
Time Frame
Up to approximately 114 months
Title
Time to biochemical progression - Randomized Phase 3
Description
Time to biochemical progression is defined as the time from randomization to the date of biochemical progression based on IRC assessment.
Time Frame
Up to approximately 114 months
Title
Safety assessment: adverse events (AEs)- Randomized Phase 3
Description
Number of participants with AEs
Time Frame
Up to approximately 144 months
Title
Plasma concentration of isatuximab- Randomized Phase 3
Description
Concentration observed just before treatment administration during repeated dosing (Ctrough) after IV administration
Time Frame
At predose of Cycle 2 Day 1 and Cycle 6 Day 1
Title
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30-Randomized Phase 3
Description
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
Time Frame
Baseline to follow-up (up to approximately 7 years)
Title
EORTC QLQ-MY20 - Randomized Phase 3
Description
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
Time Frame
Baseline to follow-up (up to approximately 7 years)
Title
EQ-5D-5L Randomized Phase 3
Description
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
Time Frame
Baseline to follow-up (up to approximately 7 years)
Title
Randomized Phase 3: HRUPQ - Randomized Phase 3
Description
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 HRSM on employment/work higher scores = greater impact on work/productivity, resources
Time Frame
Baseline to follow-up (up to approximately 7 years)
Title
Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2) Randomized Phase 3
Description
Patient's qualitative assessment of treatment will be assessed using a 10 point visual analogue/numeric rating scale with response anchors of 'not beneficial at all' to 'extremely beneficial'; higher scores represent greater patient-perceived benefits of treatment
Time Frame
End of treatment (up to approximately 5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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 Exclusion criteria: 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 disease, including: Myocardial infarction within 6 months with left ventricular dysfunction or uncontrolled ischemic cardiac disease before Cycle 1 Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV) Uncontrolled cardiac arrhythmia (Grade 2 or higher by NCI-CTCAE Version 5.0) or clinically significant electrocardiogram (ECG) abnormalities 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 HBV infection: Patients with positive HBsAg and/or HBV DNA Of note: Patient can be eligible if anti-HBc 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 HCV infection: positive HCV 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free number for US & Canada)
Phone
800-633-1610
Ext
option 6
Email
Contact-US@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
UCLA-Site Number:8400010
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Individual Site Status
Recruiting
Facility Name
Colorado Blood Cancer Institute-Site Number:8400007
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
Cancer Specialist of North Florida-Site Number:8400011
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Miami-Site Number:8400012
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana Farber Cancer Institute-Site Number:8400001
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Presbyterian Hospital-Site Number:8400015
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Name
Novant Health Forsyth Medical Center-Site Number:8401015
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology, PLLC-Site Number:8400006
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
~University of Texas - MD Anderson Cancer Center-Site Number:8400002
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0360008
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360005
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360001
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360002
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360007
City
Heidelberg West
State/Province
Victoria
ZIP/Postal Code
3081
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360004
City
Richmond
State/Province
Victoria
ZIP/Postal Code
3121
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0360006
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :0760002
City
Sao Paulo
State/Province
São Paulo
ZIP/Postal Code
04537-081
Country
Brazil
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1240004
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1240005
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C 6Z8
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1240001
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1560002
City
Hangzhou
ZIP/Postal Code
310003
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1560003
City
Hangzhou
ZIP/Postal Code
310003
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1560006
City
Nanchang
ZIP/Postal Code
330006
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1560004
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1560005
City
Shenyang
ZIP/Postal Code
110022
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :1560001
City
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2080001
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2080003
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2080005
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2080002
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500009
City
Ars-Laquenexy
ZIP/Postal Code
57085
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500010
City
Bayonne
ZIP/Postal Code
64109
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500007
City
GRENOBLE Cedex 9
ZIP/Postal Code
38043
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500006
City
La Roche sur Yon
ZIP/Postal Code
85925
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500003
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500005
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500011
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500002
City
Poitiers Cedex
ZIP/Postal Code
86021
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2500001
City
RENNES Cedex 09
ZIP/Postal Code
35033
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2760001
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :2760002
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3000002
City
Athens
ZIP/Postal Code
10676
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3000001
City
Athens
ZIP/Postal Code
11528
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3000003
City
Thessaloniki
ZIP/Postal Code
PC 54007
Country
Greece
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3480003
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3480001
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3480002
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3480004
City
Kaposvár
ZIP/Postal Code
7400
Country
Hungary
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3720003
City
Dublin 7
State/Province
Dublin
Country
Ireland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3720002
City
Dublin 8
State/Province
Dublin
Country
Ireland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3720001
City
Dublin 9
State/Province
Dublin
Country
Ireland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3760004
City
Ashdod
ZIP/Postal Code
7747629
Country
Israel
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3760001
City
Jerusalem
ZIP/Postal Code
91031
Country
Israel
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3760002
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3760005
City
Petah-Tikva
ZIP/Postal Code
49100
Country
Israel
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3760006
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3760003
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3800006
City
Meldola
State/Province
Forlì-Cesena
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3800001
City
Rozzano
State/Province
Milano
ZIP/Postal Code
20089
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3800005
City
Ancona
ZIP/Postal Code
60032
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3800003
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3800002
City
Terni
ZIP/Postal Code
05100
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3920002
City
Nagoya-shi
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3920006
City
Kamogawa-shi
State/Province
Chiba
ZIP/Postal Code
296-8602
Country
Japan
Individual Site Status
Completed
Facility Name
Investigational Site Number :3920008
City
Maebashi-shi
State/Province
Gunma
ZIP/Postal Code
371-8511
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3920005
City
Higashiibaraki-gun
State/Province
Ibaraki
ZIP/Postal Code
311-3193
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3920003
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3920009
City
Sunto-gun
State/Province
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :3920001
City
Shibuya-ku
State/Province
Tokyo
ZIP/Postal Code
150-8935
Country
Japan
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :4100004
City
Gangnam-gu
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :4100003
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :4100001
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :4100002
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :4400001
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :5540004
City
Christchurch
State/Province
Canterbury
Country
New Zealand
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :5540001
City
Hamilton
State/Province
Waikato
ZIP/Postal Code
3204
Country
New Zealand
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :5780002
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :5780001
City
Oslo
ZIP/Postal Code
0450
Country
Norway
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :6160006
City
Bydgoszcz
State/Province
Kujawsko-pomorskie
ZIP/Postal Code
85-168
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :6160002
City
Lodz
State/Province
Lódzkie
ZIP/Postal Code
93-510
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :6160008
City
Gdansk
State/Province
Pomorskie
ZIP/Postal Code
80-214
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :6160005
City
Chorzow
State/Province
Slaskie
ZIP/Postal Code
41-500
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240004
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240001
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08041
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240006
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240002
City
Valencia
State/Province
Valenciana, Comunidad
ZIP/Postal Code
46017
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240005
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240007
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7240003
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7520001
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :7520003
City
Helsingborg
ZIP/Postal Code
251 87
Country
Sweden
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :8260002
City
Bournemouth
State/Province
Hampshire
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :8260003
City
London
State/Province
London, City Of
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :8260001
City
Leicester
ZIP/Postal Code
LE15WW
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
Investigational Site Number :8260004
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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

Learn more about this trial

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

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