A Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Patients With Multicentric Castleman's Disease

• Number of patients with adverse events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  

• Number of multicentric Castleman's disease patients evaluated for assessment of atypical IL-6 splice variants or cleavage fragments [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Pharmacodynamic biomarker evaluations include assessment of atypical IL-6 splice variants or cleavage fragments.
  
  
• Number of multicentric Castleman's disease patients evaluated for assessment of C-reactive protein [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Pharmacodynamic biomarker evaluations include assessment of C-reactive protein.
  
  
• Number of previously responding multicentric Castleman's disease patients and siltuximab-naive patients who maintain disease control [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.
  
  
• Duration of multicentric Castleman's disease control [ Time Frame: Up to death ] [ Designated as safety issue: No ]
  Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.
  
  
• Duration of survival for patients with multicentric Castleman's disease [ Time Frame: Up to death ] [ Designated as safety issue: No ]
  Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.
  
  
• Multicentric Castleman's Disease Symptom Scale scores [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  Multicentric Castleman's Disease Symptom Scale scores questionnaire will only be completed by the sub-population from the C0328T03 study. These scores will be calculated as a measure of severity of symptoms.
  
  
• Assessment of glycoform clearance analysis [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
  For evaluating the clearance and degradation of glycoforms after administration of siltuximab, 6 serum samples will be collected from 5 former C0328T03 patients (a limited number of samples are needed for this analysis).
  
  
• Assessment of in vivo protein degradation analysis [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
  Siltuximab will be isolated from the serum samples using an anti-Id antibody. The purified protein will be analyzed by liquid chromatography/mass spectroscopy techniques (intact mass and peptide mapping).
  
  

This is an open-label (all people know the identity of the intervention), multicenter (study conducted in multiple sites), non-randomized (patients are not assigned by chance to treatment groups), Phase 2 study. Up to 75 patients with MCD will be eligible for the study, the majority of whom will be on active therapy with siltuximab at the time of enrollment. Patients will be either siltuximab-naive or have not progressed on siltuximab in the opinion of the investigator. Duration of disease control and survival will be assessed. Data collection for patients who discontinue treatment will be limited to survival, occurrence of malignancies, and subsequent therapies for MCD, which will be assessed twice per year until the patient has been lost to follow up or has withdrawn consent for the study, 50 percentage of the patients have died, or the end of study, whichever occurs first. An interim analysis will be conducted (no later than 2 years after the start of enrollment) to further evaluate the benefit and safety of long-term treatment with siltuximab in patients with MCD. A data cutoff (collection of last observed data of the last patient) will occur at 5 years after the start of enrollment and those patients remaining on treatment after the data cutoff, data collection will be limited to serious adverse events, concomitant medications used to treat serious adverse events, pregnancies, and survival status (twice per year). Safety evaluations for adverse events, clinical laboratory tests, vital signs, and physical examination will be performed throughout the study. The end of study is the date of the last assessment for the last patient.