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

Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: 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: \>=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. The statistical analysis shows difference in symptomatic response rate (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

Time frame: From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from study, or up to 48 weeks after last participant started study medication(approximately 3 years), whichever occurred earlier

Population: Intent-to-treat (ITT) population: all randomized participants.

Overall survival was defined as percent chance of survival of participants who were still alive at 6 years from time of first study treatment was analyzed.

Time frame: until 6 years

Population: Safety Analysis set included all randomized participants who received at least 1 dose of study agent.

Duration of tumor and symptomatic response is defined as time from first documentation of tumor and symptomatic response (CR or PR) to treatment failure. Whenever possible, treatment failure documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions. Symptomatic response is complete response (CR) + partial response (PR). CR: 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: \>=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks.

Time frame: From the date when durable tumour and symptomatic response is achieved until treatment failure, as assessed until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: All randomized participants who achieved durable tumor and symptomatic response during blinded treatment period as per independent review.

Duration of tumor response is defined as time from first documentation of tumor response to tumor progression. Tumour response is complete response (CR) + partial response (PR) as assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a \>=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

Time frame: From the date when tumour response is achieved until tumour progression, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years)

Population: All randomized participants who achieved tumor response during blinded treatment period as per independent review.

A patient-reported symptom scale. Symptom presence/absence and severity are noted on an anchor-based numeric scale. Scores range from 1 (very mild) to 5 (very severe).

Time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Intent-to-treat (ITT) population: all randomized participants.

The FACIT-F, a 13-item instrument, was designed to measure patient-reported fatigue. It is one of the suite of FACIT instruments developed for outcomes in cancer. Concepts measured in the scale include tiredness, weakness, and difficulty conducting usual functional activities or social interaction due to fatigue. Response options range from not at all (0) to very much (4), and yield a summary score. Total FACIT-F score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes.

Time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Intent-to-treat (ITT) population: all randomized participants.

SF-36 is a questionnaire and PCS is a part of subscale assessing physical functioning, role-physical, bodily pain, and general health. The scores range from 0 (worst score) to 100 (best score), with a higher score indicating better quality of life.

Time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Intent-to-treat (ITT) population: all randomized participants.

Hemoglobin response rate is defined as percentage of participants who achieved \>= 20 g/L hemoglobin at Week 13.

Time frame: Week 13

Population: Hemoglobin response-evaluable population: participants who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 post-baseline hemoglobin evaluation.

Overall tumor response is CR + PR assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a \>=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care \[BSC\] minus Placebo+BSC).

Time frame: From Day 1 of Cycle 1 until the date when durable tumour and symptomatic response is achieved, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years)

Population: Response-evaluable Population: included participants who received at least 1 administration of siltuximab/placebo and had at least 1 post-baseline radiologic disease evaluation.

Hemoglobin response rate is defined as percentage of participants who achieved \>= 15 g/L hemoglobin at Week 13.

Time frame: Week 13

Population: Hemoglobin response-evaluable population: participants who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 postbaseline hemoglobin evaluation.

Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).

Time frame: From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment (approximately 3 years)

Population: All randomized participants who were dependent on corticosteroids at baseline.

Time to treatment failure was defined as the time from randomization until the participant fails treatment. Treatment failure was defined as any of the following: a sustained increase from baseline in disease related symptoms \>=Grade 2 persisting for at least 3 weeks despite best supportive care (BSC); onset of any new disease related Grade 3 or higher symptom despite BSC; sustained (ie, at least 3 weeks) deterioration in performance status (increase from baseline in Eastern Cooperative Oncology Group Performance Status by more than 1 point) despite BSC; radiologic progression, as measured by modified Cheson criteria; Initiation of any other therapy intended to treat multicentric Castleman's disease ie, prohibited treatments. Statistical analysis shows difference in treatment failure rate (siltuximab+BSC minus Placebo+BSC).

Time frame: From the date of randomization until a participant fails treatment, as assessed up to 48 weeks after the last participant started study treatment (approximately 3 years), whichever occurred earlier

Population: Intent-to-treat (ITT) population: all randomized participants.