A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma

• One-year progression-free survival (PFS) rate [ Time Frame: One year after randomization of last patient ] [ Designated as safety issue: No ]
  Defined by CRAB - IMWG (calcium, renal, anemia, and bone lesions - International Myeloma Working Group) criteria.
  
  

• Progression-free survival (PFS) [ Time Frame: Up to approximately 4 years after randomization of last patient ] [ Designated as safety issue: No ]
  Based on CRAB criteria.
  
  
• Progressive Disease (PD) indicator rate [ Time Frame: 6 months after randomization of last patient ] [ Designated as safety issue: No ]
  Novel composite endpoint, built from potential early signs of progression to multiple myeloma.
  
  
• European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) [ Time Frame: Up to approximately 4 years after randomization of last patient ] [ Designated as safety issue: No ]
  The questionnaire includes 9 scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 6 single-item scales (dyspnea, insomnia, anorexia, constipation, diarrhea and financial impact) and single-item global health and quality of life scales.
  
  
• Brief Pain Inventory (worst pain item) [ Time Frame: Up to approximately 4 years after randomization of last patient ] [ Designated as safety issue: No ]
  Refers to the "worst" pain the patient has experienced over the past 24 hours.
  
  
• Changes in clinical laboratory values [ Time Frame: Up to approximately 4 years after randomization of last patient ] [ Designated as safety issue: Yes ]
  
• Number of participants experiencing adverse events [ Time Frame: Up to approximately 4 years after randomization of last patient ] [ Designated as safety issue: Yes ]
  
• Overall survival [ Time Frame: Approximately 4 years after randomization of last patient ] [ Designated as safety issue: No ]
  

This is a randomized (treatment assigned by chance), double-blind (neither patient nor investigator know which treatment is given), multicenter study to evaluate the safety and efficacy of siltuximab compared with placebo in patients with high-risk SMM (defined as bone marrow plasma cells >=10% and either serum monoclonal protein >=3 g/dL, or abnormal free light chain ratio <0.126 or >8 and serum M-protein <3 g/dL but >=1 g/dL). Approximately 100 patients will receive either siltuximab or placebo by intravenous (IV, injection into a vein) infusion every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study (approximately 4 years after randomization of the last patient). Efficacy, pharmacokinetics, immunogenicity, and potential biomarkers will be assessed at time points defined in the protocol. Patient reported outcomes (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30, Brief Pain Inventory [worst pain], Non-Chemotherapy Anemia Symptom Scale) will be administered before any procedure or treatment at each visit. Patient safety will be monitored throughout the study.