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
a study on Multiple Myeloma
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Healthy Volunteers
- healthy people welcome
- Location
- at Los Angeles, California and other locations
- Dates
- study startedcompletion around
- Principal Investigator
- by Sarah Larson
Description
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)
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
Details
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.
Keywords
Plasma Cell Myeloma, Anti-CD38 monoclonal antibody, Multiple Myeloma, Plasma Cell Neoplasms, Smoldering Multiple Myeloma, Acetaminophen, Diphenhydramine, Promethazine, Dexamethasone, Methylprednisolone, Lenalidomide, Montelukast, Isatuximab SAR650984, Montelukast or equivalent, Diphenhydramine or equivalent, Methylprednisolone or equivalent, Isatuximab, lenalidomide, and dexamethasone (ILd), Lenalidomide and dexamethasone (Ld)
Eligibility
You can join if…
Open to people ages 18 years and up
- 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
You CAN'T join if...
- 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.
Locations
- UCLA Site Number : 8400010
Los Angeles California 90024 United States - Colorado Blood Cancer Institute Site Number : 8400007
Denver Colorado 80218 United States
Lead Scientist at UCLA
- Sarah Larson
HS Associate Clinical Professor, Medicine. Authored (or co-authored) 19 research publications
Details
- Status
- in progress, not accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Sanofi
- ID
- NCT04270409
- Phase
- Phase 3 Multiple Myeloma Research Study
- Study Type
- Interventional
- Participants
- Expecting 337 study participants
- Last Updated