NCT04270409

Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma

A Phase 3 Randomized, Open-label, Multicenter Study of Isatuximab (SAR650984) in Combination With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With High-risk Smoldering Multiple Myeloma

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 337 (actual)
• Sponsor: Sanofi · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Primary Objectives: * Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM) * Randomized Phase 3 Part: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression-free survival when compared to lenalidomide and dexamethasone in subjects with high-risk SMM Secondary Objectives: Safety run-in Part: * To assess overall response rate (ORR) * To assess duration of response (DOR) * To assess minimal residual disease (MRD) negativity in participants achieving very good partial response (VGPR) or complete response (CR) * To assess time to diagnostic (SLiM CRAB) progression or death * To assess time to first-line treatment for multiple myeloma (MM) * To assess the potential immunogenicity of isatuximab * Impact of abnormal chromosomal subtype on participant outcome Randomized Phase 3 Part: Key Secondary Objectives: To compare between the arms * MRD negativity * Sustained MRD negativity * Second progression-free survival (PFS2) * Overall survival Other Secondary Objectives: To evaluate in both arms * CR rate * ORR * DOR * Time to diagnostic (SLiM CRAB) progression * Time to biochemical progression * Time to first-line treatment for MM * Impact of abnormal chromosomal subtype on participant outcome * Safety and tolerability * Pharmacokinetics (PK) * Potential of isatuximab immunogenicity * Clinical outcome assessments (COAs)

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

Interventions

Type	Name	Description
DRUG	Isatuximab SAR650984	Pharmaceutical for: Solution for infusion Route of administration: Intravenous
DRUG	Lenalidomide	Pharmaceutical form: Capsules Route of administration: Oral
DRUG	Dexamethasone	Pharmaceutical form: Tablets and solution for injection Route of administration: Oral and intravenous
DRUG	Montelukast or equivalent	Auxiliary Medicinal Product (AxMP)/pre-medication; ATC code: R03DC03; Pharmaceutical form: tablet; Route of administration: Oral;
DRUG	Acetaminophen	AxMP/pre-medication ATC code: N02BE01 Pharmaceutical form: tablet/ampule/capsule; Route of administration: Intravenous (IV) or per os (PO)
DRUG	Diphenhydramine or equivalent	AxMP/pre-medication ATC code: R06AA02 Pharmaceutical form: ampule; Route of administration: Intravenous
DRUG	Methylprednisolone or equivalent	AxMP/pre-medication; ATC code: H02AB04; Pharmaceutical form: vial; Route of administration: Intravenous

Timeline

• Start date: 2020-06-16
• Primary completion: 2030-10-14
• Completion: 2033-10-21
• First posted: 2020-02-17
• Last updated: 2025-12-12

Locations

105 sites across 24 countries: United States, Australia, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Lithuania, New Zealand, Norway, Poland, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study