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)

View Full Description

Full 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.

View Eligibility Criteria

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 mLmin1.73 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 gdL or both) transfusion support 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.

Study is for people with:

Multiple Myeloma

Phase:

Phase 3

Estimated Enrollment:

300

Study ID:

NCT04270409

Recruitment Status:

Recruiting

Sponsor:

Sanofi

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There are 101 Locations for this study

See Locations Near You

UCLA-Site Number:8400010
Los Angeles California, 90024, United States
Colorado Blood Cancer Institute-Site Number:8400007
Denver Colorado, 80218, United States
Cancer Specialist of North Florida-Site Number:8400011
Jacksonville Florida, 32256, United States
University of Miami-Site Number:8400012
Miami Florida, 33136, United States
Dana Farber Cancer Institute-Site Number:8400001
Boston Massachusetts, 02115, United States
Presbyterian Hospital-Site Number:8400015
Charlotte North Carolina, 28204, United States
Novant Health Forsyth Medical Center-Site Number:8401015
Winston-Salem North Carolina, 27103, United States
Tennessee Oncology, PLLC-Site Number:8400006
Nashville Tennessee, 37203, United States
~University of Texas - MD Anderson Cancer Center-Site Number:8400002
Houston Texas, 77030, United States
Investigational Site Number :0360008
Liverpool New South Wales, 2170, Australia
Investigational Site Number :0360005
Waratah New South Wales, 2298, Australia
Investigational Site Number :0360001
Wollongong New South Wales, 2500, Australia
Investigational Site Number :0360002
Fitzroy Victoria, 3065, Australia
Investigational Site Number :0360007
Heidelberg West Victoria, 3081, Australia
Investigational Site Number :0360004
Richmond Victoria, 3121, Australia
Investigational Site Number :0360006
Nedlands Western Australia, 6009, Australia
Investigational Site Number :0760002
Sao Paulo São Paulo, 04537, Brazil
Investigational Site Number :1240004
Edmonton Alberta, T6G 1, Canada
Investigational Site Number :1240005
Moncton New Brunswick, E1C 6, Canada
Investigational Site Number :1240001
Montreal Quebec, H1T 2, Canada
Investigational Site Number :1560002
Hangzhou , 31000, China
Investigational Site Number :1560003
Hangzhou , 31000, China
Investigational Site Number :1560006
Nanchang , 33000, China
Investigational Site Number :1560004
Shanghai , 20003, China
Investigational Site Number :1560005
Shenyang , 11002, China
Investigational Site Number :1560001
Tianjin , 30002, China
Investigational Site Number :2030004
Brno , 62500, Czechia
Investigational Site Number :2030005
Hradec Kralove , 50005, Czechia
Investigational Site Number :2030002
Olomouc , 77900, Czechia
Investigational Site Number :2030003
Ostrava - Poruba , 70852, Czechia
Investigational Site Number :2030001
Praha 2 , 12808, Czechia
Investigational Site Number :2080001
Aalborg , 9000, Denmark
Investigational Site Number :2080003
Aarhus N , 8200, Denmark
Investigational Site Number :2080005
Copenhagen , 2100, Denmark
Investigational Site Number :2080002
Roskilde , 4000, Denmark
Investigational Site Number :2500009
Ars-Laquenexy , 57085, France
Investigational Site Number :2500010
Bayonne Cedec , 64109, France
Investigational Site Number :2500007
GRENOBLE Cedex 9 , 38043, France
Investigational Site Number :2500006
La Roche sur Yon , 85925, France
Investigational Site Number :2500003
Lille , 59037, France
Investigational Site Number :2500005
Paris , 75012, France
Investigational Site Number :2500011
Paris , 75013, France
Investigational Site Number :2500002
Poitiers Cedex , 86021, France
Investigational Site Number :2500001
RENNES Cedex 09 , 35033, France
Investigational Site Number :2760001
Hamburg , 20246, Germany
Investigational Site Number :2760002
Heidelberg , 69120, Germany
Investigational Site Number :3000002
Athens , 10676, Greece
Investigational Site Number :3000001
Athens , 11528, Greece
Investigational Site Number :3000003
Thessaloniki , PC 54, Greece
Investigational Site Number :3480003
Budapest , 1083, Hungary
Investigational Site Number :3480001
Budapest , 1097, Hungary
Investigational Site Number :3480002
Debrecen , 4032, Hungary
Investigational Site Number :3480004
Kaposvár , 7400, Hungary
Investigational Site Number :3720003
Dublin 7 Dublin, , Ireland
Investigational Site Number :3720002
Dublin 8 Dublin, , Ireland
Investigational Site Number :3720001
Dublin 9 Dublin, , Ireland
Investigational Site Number :3760004
Ashdod , 77476, Israel
Investigational Site Number :3760001
Jerusalem , 91031, Israel
Investigational Site Number :3760002
Jerusalem , 91120, Israel
Investigational Site Number :3760005
Petah-Tikva , 49100, Israel
Investigational Site Number :3760006
Ramat Gan , 52656, Israel
Investigational Site Number :3760003
Tel Aviv , 64239, Israel
Investigational Site Number :3800006
Meldola Forlì-Cesena, 47014, Italy
Investigational Site Number :3800001
Rozzano Milano, 20089, Italy
Investigational Site Number :3800005
Ancona , 60032, Italy
Investigational Site Number :3800003
Bologna , 40138, Italy
Investigational Site Number :3800002
Terni , 05100, Italy
Investigational Site Number :3920002
Nagoya-shi Aichi, 467-8, Japan
Investigational Site Number :3920006
Kamogawa-shi Chiba, 296-8, Japan
Investigational Site Number :3920008
Maebashi-shi Gunma, 371-8, Japan
Investigational Site Number :3920010
Sapporo-shi Hokkaido, 060-8, Japan
Investigational Site Number :3920005
Higashiibaraki-gun Ibaraki, 311-3, Japan
Investigational Site Number :3920004
Konan-ku, Yokohama-shi Kanagawa, 234-0, Japan
Investigational Site Number :3920003
Okayama-shi Okayama, 701-1, Japan
Investigational Site Number :3920007
Osaka-shi Osaka, 543-8, Japan
Investigational Site Number :3920009
Sunto-gun Shizuoka, 411-8, Japan
Investigational Site Number :3920001
Shibuya-ku Tokyo, 150-8, Japan
Investigational Site Number :4100004
Gangnam-gu Seoul-teukbyeolsi, 06351, Korea, Republic of
Investigational Site Number :4100003
Seoul Seoul-teukbyeolsi, 03080, Korea, Republic of
Investigational Site Number :4100001
Seoul Seoul-teukbyeolsi, 03722, Korea, Republic of
Investigational Site Number :4100002
Seoul , 06591, Korea, Republic of
Investigational Site Number :4400001
Vilnius , 08661, Lithuania
Investigational Site Number :5540004
Christchurch Canterbury, , New Zealand
Investigational Site Number :5540001
Hamilton Waikato, 3204, New Zealand
Investigational Site Number :5780002
Bergen , 5021, Norway
Investigational Site Number :5780001
Oslo , 0450, Norway
Investigational Site Number :6160006
Bydgoszcz Kujawsko-pomorskie, 85-16, Poland
Investigational Site Number :6160002
Lodz Lódzkie, 93-51, Poland
Investigational Site Number :6160008
Gdansk Pomorskie, 80-21, Poland
Investigational Site Number :6160005
Chorzow Slaskie, 41-50, Poland
Investigational Site Number :7240004
Barcelona Barcelona [Barcelona], 08036, Spain
Investigational Site Number :7240001
Barcelona Barcelona [Barcelona], 08041, Spain
Investigational Site Number :7240005
Madrid Madrid, Comunidad De, 28041, Spain
Investigational Site Number :7240006
Pamplona Navarra, 31008, Spain
Investigational Site Number :7240002
Valencia Valenciana, Comunidad, 46017, Spain
Investigational Site Number :7240007
Salamanca , 37007, Spain
Investigational Site Number :7240003
Zaragoza , 50009, Spain
Investigational Site Number :7520001
Göteborg , 413 4, Sweden
Investigational Site Number :7520003
Helsingborg , 251 8, Sweden
Investigational Site Number :7920005
Ankara , 06010, Turkey
Investigational Site Number :7920001
Ankara , , Turkey
Investigational Site Number :7920004
Istanbul , 34214, Turkey
Investigational Site Number :7920002
Istanbul , 34390, Turkey
Investigational Site Number :7920003
Izmir , 35040, Turkey
Investigational Site Number :8260002
Bournemouth Hampshire, BH7 7, United Kingdom
Investigational Site Number :8260003
London London, City Of, SE1 7, United Kingdom
Investigational Site Number :8260001
Leicester , LE15W, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 3

Estimated Enrollment:

300

Study ID:

NCT04270409

Recruitment Status:

Recruiting

Sponsor:


Sanofi

How clear is this clinincal trial information?

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