A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease

• Number of patients that achieve a tumor and symptomatic response [ Time Frame: Up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  Tumor and symptomatic response may be either a complete response (CR) or a partial response (PR). CR is defined as a complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to Multicentric Castleman's disease, sustained for at least 18 weeks. PR is defined as a greater than or equal to 50% decrease in sum of the product of the diameters (SPD) of index lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure, sustained for at least 18 weeks.
  
  

• Duration of tumor and symptomatic response [ Time Frame: Up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  It is defined as time from first documentation of tumor and symptomatic response (CR or PR) to treatment failure.
  
  
• Number of patients with tumor response [ Time Frame: Up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  Tumor response is based on the assessment of index lesions (measurable) and nonindex lesions (non measurable).
  
  
• Duration of Tumor Response [ Time Frame: Up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  It is defined as time from first documentation of tumor response (CR or PR) to tumor progression.
  
  
• Time to Treatment Failure [ Time Frame: Up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  It is defined as the time from randomization to treatment failure.
  
  
• Maximum change from baseline in hemoglobin value [ Time Frame: Baseline up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  Change in hemoglobin will be calculated as maximum change from baseline (in hemoglobin value) in the absence of transfusion.
  
  
• Number of patients that discontinued corticosteroid therapy [ Time Frame: Up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  These are the number of patients who are able to discontinue corticosteroids, if they were corticosteroid dependent at study entry.
  
  
• Change from baseline in relevant patient reported outcome scales [ Time Frame: Baseline up to 48 weeks after the last patient begins study treatment ] [ Designated as safety issue: No ]
  Changes versus baseline will be compared between cohorts.
  
  
• Maximum observed serum concentration of CNTO 328 [ Time Frame: Up to 12 weeks after administration of last study drug infusion ] [ Designated as safety issue: No ]
  Maximum observed serum concentration of CNTO 328 will be measured when CNTO 328 is administered intravenously along with best supportive care.
  
  
• Minimum observed serum concentration of CNTO 328 [ Time Frame: Up to 12 weeks after administration of last study drug infusion ] [ Designated as safety issue: No ]
  Minimum observed serum concentration of CNTO 328 will be measured when CNTO 328 is administered intravenously along with best supportive care.
  
  
• Area under the serum concentration versus time curve of CNTO 328 [ Time Frame: Up to 12 weeks after administration of last study drug infusion ] [ Designated as safety issue: No ]
  Area under the serum concentration versus time curve of CNTO 328 will be measured when CNTO 328 is administered intravenously along with best supportive care.
  
  
• Half-life of CNTO 328 [ Time Frame: Up to 12 weeks after administration of last study drug infusion ] [ Designated as safety issue: No ]
  Half-life of CNTO 328 will be measured when CNTO 328 is administered intravenously along with best supportive care.
  
  
• Volume of distribution of CNTO 328 [ Time Frame: Up to 12 weeks after administration of last study drug infusion ] [ Designated as safety issue: No ]
  Volume of distribution of CNTO 328 will be measured when CNTO 328 is administered intravenously along with best supportive care.
  
  
• Number of patients with antibodies to CNTO 328 [ Time Frame: Up to 12 weeks after administration of last study drug infusion ] [ Designated as safety issue: No ]
  Antibodies to CNTO 328 will be detected using a validated immunoassay. All samples collected for detection of antibodies to CNTO 328 will also be evaluated for CNTO 328 serum concentration to interpret antibody response data.
  
  
• Number of patients with adverse events [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  

This is a multicenter (study conducted at multiple sites), randomized (the study medication is assigned by chance), double blind (neither investigator nor the participant knows the treatment that the participant receives), placebo controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), study to assess the efficacy and safety of CNTO 328 plus BSC compared with BSC in patients with symptomatic Multicentric Castleman's Disease. The study mainly consists of 3 phases, including: the screening phase (majority of assessments performed within 28 days of first dose), the treatment phase, and the follow up phase. In the treatment phase, approximately 78 patients will be randomly assigned in 1:2 ratios to either of 2 treatment groups, ie, Treatment Group A: Placebo + BSC, or Treatment Group B: CNTO 328 + BSC. The follow up phase will be 3 months after last dose of study medication and the survival will be followed up until the study ends. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, patient-recorded temperature, and physical examination will be monitored throughout the study. The total study duration will be 5 years after the last patient starts study medication.