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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety of siltuximab in patients with multicentric Castleman's disease (MCD).

Detailed Description
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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 2b 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subsequent therapies for MCD, which will be assessed twice per year until the patient has been lost to follow up or has withdrawn consent for the study, whichever occurs first.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 will occur at 6 years after the start of enrollment and for those patients remaining on treatment after the data cutoff, data collection will be limited to pregnancies and serious adverse events (SAEs), including information on study agent administration and concomitant medications associated with an SAE. 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.

Official Title
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An Open-label, Multicenter Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Subjects With Multicentric Castleman's Disease

Conditions
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Multicentric Castleman's Disease

Intervention / Treatment
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* Drug: Siltuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has multicentric Castleman's disease Have previously been enrolled in Study C0328T03 or CNTO328MCD2001 (either treatment arm) Have had their last administration of study treatment (siltuximab or placebo) less than 6 weeks (window of plus 2 weeks) prior to first dose Patients must not have had disease progression while receiving siltuximab. For those patients originally assigned to placebo in the CNTO328MCD2001 study, patients who have received less than 4 months of siltuximab following crossover will also be eligible Have adequate clinical laboratory parameters within 2 weeks prior to the first dose of siltuximab for this study Exclusion Criteria: Unmanageable toxicity, an adverse event, progression of disease, or withdrawal of consent as reason for discontinuing treatment from previous sponsor-initiated siltuximab study Vaccination with live, attenuated vaccines within 4 weeks of first dose of this study Known unmanageable allergies, hypersensitivity, intolerance to monoclonal antibodies, to murine, chimeric, human proteins or their excipients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Siltuximab<br>Siltuximab 11 mg/kg, intravenous infusion, given as a 1-hour infusion every 3 weeks. | Drug: Siltuximab<br>* Type=exact number, unit=mg/kg, number=11, form=intravenous solution, route=intravenous. Siltuximab given as a 1-hour infusion every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Previously Responding Participants Who Maintained Disease Control | Percentage of participants maintaining disease control (defined as stable or better response) was defined as the percentage of previously responding participants who had not progressed during the long-term safety extension based on investigator assessment. A worsening in any of the measures will be considered as a progression of the disease. | Up to 6 years | 
| Percentage of Siltuximab-naive Participants Who Experienced Disease Control | Percentage of participants experiencing disease control was defined as the percentage of siltuximab-naïve participants who had stable or better response during the long-term safety extension based on investigator's judgment. Disease control was defined as stable or better response assessed by the investigators. | Up to 6 years | 
| Duration of Disease Control | Duration of disease control (DODC) was defined as the time from the first siltuximab administration in this study to disease progression as assessed by the investigator. Disease control was defined as stable or better response assessed by the investigators. Kaplan-Meier method was used to estimate the duration of disease control. | Up to 6 years | 
| Overall Survival | Overall survival was defined as the time between the first study siltuximab administration and death due to any cause. Kaplan-Meier method was used to estimate the overall survival. | Up to 6 years | 
| Number of Participants Positive for Antibodies to Siltuximab | Serum samples were screened for antibodies binding to siltuximab and number of participants positive for antibodies to siltuximab was reported. | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multicentric Castleman's Disease, Multicentric, Castleman, Siltuximab, Long term safety