Multiple Myeloma Clinical 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
Summary
Primary Objectives:
Safety run-in: To confirm the recommended dose of treatment-a-promising-new-option-for-relapsed-multiple-myeloma/" >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)
Full 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.
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.
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 90 Locations for this study
Los Angeles California, 90024, United States
Denver Colorado, 80218, United States
Jacksonville Florida, 32256, United States
Miami Florida, 33136, United States
Boston Massachusetts, 02115, United States
Charlotte North Carolina, 28204, United States
Winston-Salem North Carolina, 27103, United States
Nashville Tennessee, 37203, United States
Houston Texas, 77030, United States
Liverpool New South Wales, 2170, Australia
Waratah New South Wales, 2298, Australia
Wollongong New South Wales, 2500, Australia
Fitzroy Victoria, 3065, Australia
Heidelberg West Victoria, 3081, Australia
Richmond Victoria, 3121, Australia
Nedlands Western Australia, 6009, Australia
Sao Paulo São Paulo, 04537, Brazil
Edmonton Alberta, T6G 1, Canada
Moncton New Brunswick, E1C 6, Canada
Montreal Quebec, H1T 2, Canada
Hangzhou , 31000, China
Hangzhou , 31000, China
Nanchang , 33000, China
Shanghai , 20003, China
Shenyang , 11002, China
Tianjin , 30002, China
Aalborg , 9000, Denmark
Aarhus N , 8200, Denmark
Copenhagen , 2100, Denmark
Roskilde , 4000, Denmark
Ars-Laquenexy , 57085, France
Bayonne , 64109, France
GRENOBLE Cedex 9 , 38043, France
La Roche sur Yon , 85925, France
Lille , 59037, France
Paris , 75012, France
Paris , 75013, France
Poitiers Cedex , 86021, France
RENNES Cedex 09 , 35033, France
Hamburg , 20246, Germany
Heidelberg , 69120, Germany
Athens , 10676, Greece
Athens , 11528, Greece
Thessaloniki , PC 54, Greece
Budapest , 1083, Hungary
Budapest , 1097, Hungary
Debrecen , 4032, Hungary
Kaposvár , 7400, Hungary
Dublin 7 Dublin, , Ireland
Dublin 8 Dublin, , Ireland
Dublin 9 Dublin, , Ireland
Ashdod , 77476, Israel
Jerusalem , 91031, Israel
Jerusalem , 91120, Israel
Petah-Tikva , 49100, Israel
Ramat Gan , 52656, Israel
Tel Aviv , 64239, Israel
Meldola Forlì-Cesena, 47014, Italy
Rozzano Milano, 20089, Italy
Ancona , 60032, Italy
Bologna , 40138, Italy
Terni , 05100, Italy
Nagoya-shi Aichi, 467-8, Japan
Kamogawa-shi Chiba, 296-8, Japan
Maebashi-shi Gunma, 371-8, Japan
Higashiibaraki-gun Ibaraki, 311-3, Japan
Okayama-shi Okayama, 701-1, Japan
Sunto-gun Shizuoka, 411-8, Japan
Shibuya-ku Tokyo, 150-8, Japan
Gangnam-gu Seoul-teukbyeolsi, 06351, Korea, Republic of
Seoul Seoul-teukbyeolsi, 03080, Korea, Republic of
Seoul Seoul-teukbyeolsi, 03722, Korea, Republic of
Seoul , 06591, Korea, Republic of
Vilnius , 08661, Lithuania
Christchurch Canterbury, , New Zealand
Hamilton Waikato, 3204, New Zealand
Bergen , 5021, Norway
Oslo , 0450, Norway
Bydgoszcz Kujawsko-pomorskie, 85-16, Poland
Lodz Lódzkie, 93-51, Poland
Gdansk Pomorskie, 80-21, Poland
Chorzow Slaskie, 41-50, Poland
Barcelona Barcelona [Barcelona], 08036, Spain
Barcelona Barcelona [Barcelona], 08041, Spain
Pamplona Navarra, 31008, Spain
Valencia Valenciana, Comunidad, 46017, Spain
Madrid , 28041, Spain
Salamanca , 37007, Spain
Zaragoza , 50009, Spain
Göteborg , 413 4, Sweden
Helsingborg , 251 8, Sweden
Bournemouth Hampshire, BH7 7, United Kingdom
London London, City Of, SE1 7, United Kingdom
Leicester , LE15W, United Kingdom
Southampton , SO16 , United Kingdom
How clear is this clinincal trial information?