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

STATUS

Recruiting
End date

May 12, 2033
participants needed

300
sponsor

Sanofi

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Updated on 19 February 2024

See if I qualify

dexamethasone

multiple myeloma

lenalidomide

bone marrow procedure

residual tumor

isatuximab

minimal residual disease

residual disease

smoldering myeloma

bone marrow plasma cells

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

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 first-line treatment for MM
Safety and tolerability
Pharmacokinetics (PK)
Potential of isatuximab immunogenicity
Clinical outcome assessments (COAs)

Description

Study duration is expected to be approximately 10 years, including a 28-day screening period, followed by an up to 36-month treatment period, and a follow-up period of approximately 7 years.

Details

Condition	Multiple Myeloma, Multiple Myeloma, Lymphoproliferative Disorder, lymphoproliferative disorders, lymphoproliferative disorders
Age	18-100 years
Treatment	Lenalidomide, Dexamethasone, Isatuximab SAR650984
Clinical Study Identifier	NCT04270409
Sponsor	Sanofi
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
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 m (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
	bone lytic lesion
	BMPCs 60%
	Serum involved/uninvolved FLC ratio 100
	Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 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 patient's potential participation in a clinical trial

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minimal residual disease

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bone marrow plasma cells

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