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

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 500

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
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion Criteria

-Evidence of any of the following CRAB criteria or Myeloma Defining Events(SLiM CRAB)detailed below attributable to the particip.SMM involvement
Increased Ca levels:Corrected serum Ca>1mg/dL above ULN or >11mg/dL
Renal insufficiency:Determined by GFR<40mL/min/1.73m² (Modification of Diet in Renal Disease[MDRD]Formula) or serum creatinine>2mg/dL
Anemia(hemoglobin 2g/dL below LLN or <10g/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
WB-MRI or PET-CT with more than 1 focal lesion(>=5mm in diameter by MRI)
-Primary systemic amyloid light-chain amyloidosis,MGUS,standard risk smoldering myeloma,soft-tissue plasmacytoma,symptomatic myeloma
-Uncontroll.infect.within 28 days prior to random.in Ph.3 or 1st study interv. admin. in safety run-in
-Clinically signific.cardiac or vascular dis. within 3 months prior to random., 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 Ver.5.0)
-Known AIDS-related illness or known HIV dis. requiring antiviral treatm. or active hepatitis A(defined as positive HA antigen or posit.IgM).HIV serology at screen.will be tested for German particip.and any other country where required as per local regul.and serology hepatitis B and C at screen.will be tested for all particip.
-Uncontroll.or active HBV infection:Patients with posit.HBsAg and/or HBV DNA
Note:
·Patient can be eligible if anti-HBc IgG posit.(with or without posit.anti-HBs)but HBsAg and HBV DNA are negat.If anti-HBV therapy in relation with prior infect.was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatm.period
·Patients with negat.HBsAg and posit.HBV DNA observed during screen.period will be evaluated by a specialist for start of anti-viral treatm:study treatm.could be proposed if HBV DNA becomes negat.and all the other study criteria are still met.
-Active HCV infect.:posit.HCV RNA and negat.anti-HCV
Note:
·Patients with antiviral therapy for HCV started before initiation of IMP and posit.HCV Ab are eligible.The antiviral therapy for HCV should continue throughout the treatm.period until seroconversion.
·Patients with posit.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 random.(or 1st study interv.admin. 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 treatm.(eg surgery,radiotherapy,medication) for a malignancy within 3 years of random.(or 1st study interv.admin. in safety run-in cohort)
-Prior exposure to approved or investigational treatm. for SMM or MM(including but not limited to conventional chemotherapies,immunomodulatory imid drugs or Proteasome inhibitors); concurrent use of bisphosphonates or RANKL inhibitor denosumab is not permitted; however, prior bisphosphonates or once-a-year IV bisph

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

Related Trials