Isatuximab in combination with lenalidomide and dexamethasone in high-risk smoldering multiple myeloma

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 565

Inclusion Criteria

- Participant must be at least 18 years of age inclusive or older
- 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
- Absolute neutrophil count (ANC) =1000/µL (1 × 109/L)
- Platelets =50,000/µL (50 × 109/L)
-> Total bilirubin =3 mg/dL (except Gilbert syndrome, in which direct
bilirubin should be =5 mg/dL)
-> Alanine aminotransferase =3× upper limit of normal (ULN), aspartate
aminotransferase = 3 × ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 367
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 198

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 = 5mm in size
*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 and localized amyloid light-chain (AL) amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, soft-tissue plasmacytoma, and 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 or vascular disease within 3 months prior to randomization, e.g. Myocardial Infarction; Unstable Angina; Coronary (e.g. Coronary Artery Bypass Graft, Percutaneous Coronary Intervention) or peripheral artery revascularization, Left Ventricular Ejection Fraction <40%, Heart Failure NYHA III-IV, Stroke, Transient Ischemic Attack, Pulmonary Embolism, other thromboembolic event, cardiac arrhythmia (Grade 3 or higher by NCI-CTCAE Version 5.0)
- 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
resistan

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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