Multicentric Castleman's Disease
Conditions
Keywords
Multicentric Castleman's Disease, Multicentric, Castleman, Siltuximab, Long term safety
Brief summary
The purpose of this study is to evaluate the long-term safety of siltuximab in patients with multicentric Castleman's disease (MCD).
Detailed description
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subsequent therapies for MCD, which will be assessed twice per year until the patient has been lost to follow up or has withdrawn consent for the study, whichever occurs first.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.
Interventions
DRUGSiltuximab
Type=exact number, unit=mg/kg, number=11, form=intravenous solution, route=intravenous. Siltuximab given as a 1-hour infusion every 3 weeks.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 6 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Previously Responding Participants Who Maintained Disease Control | Up to 6 years | 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. |
| Percentage of Siltuximab-naive Participants Who Experienced Disease Control | Up to 6 years | 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. |
| Duration of Disease Control | Up to 6 years | 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. |
| Overall Survival | Up to 6 years | 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. |
| Number of Participants Positive for Antibodies to Siltuximab | Up to 6 years | Serum samples were screened for antibodies binding to siltuximab and number of participants positive for antibodies to siltuximab was reported. |
Countries
Belgium, Brazil, Canada, China, Egypt, France, Germany, Hong Kong, Israel, New Zealand, Norway, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Participants enrolled in this study CNTO328MCD2002 included participants who were previously enrolled in study C0328T03 (NCT00412321) or CNTO328MCD2001 (NCT01024036) (either placebo or siltuximab treatment arm). A total of 60 participants from previous MCD studies C0328T03 and CNTO328MCD2001 were found eligible to be enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Siltuximab Participants received siltuximab 11 milligram per kilogram (mg/kg) as a 1-hour intravenous infusion every 3 weeks until disease progression, withdrew, experienced unacceptable toxicity,or until the 6-year data cutoff, whichever occurred first. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 1 |
| Overall Study | Study Terminated by Sponsor | 58 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Siltuximab |
|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 14.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment Belgium | 1 Participants |
| Region of Enrollment Brazil | 1 Participants |
| Region of Enrollment Canada | 1 Participants |
| Region of Enrollment China | 6 Participants |
| Region of Enrollment Egypt | 1 Participants |
| Region of Enrollment France | 3 Participants |
| Region of Enrollment Germany | 1 Participants |
| Region of Enrollment Hong Kong | 3 Participants |
| Region of Enrollment Korea, Republic Of | 4 Participants |
| Region of Enrollment New Zealand | 2 Participants |
| Region of Enrollment Norway | 2 Participants |
| Region of Enrollment Singapore | 3 Participants |
| Region of Enrollment Spain | 2 Participants |
| Region of Enrollment Taiwan, Province Of China | 1 Participants |
| Region of Enrollment United Kingdom | 2 Participants |
| Region of Enrollment United States | 27 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 60 |
| other Total, other adverse events | 60 / 60 |
| serious Total, serious adverse events | 25 / 60 |
Outcome results
Primary
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.
Time frame: Up to 6 years
Population: Safety analysis set included all enrolled participants in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Siltuximab | Number of Participants With Adverse Events (AEs) | 60 Participants |
Secondary
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.
Time frame: Up to 6 years
Population: Safety analysis set included all enrolled participants in this study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Siltuximab | Duration of Disease Control | NA years |
Secondary
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.
Time frame: Up to 6 years
Population: Safety analysis set included all enrolled participants in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Siltuximab | Number of Participants Positive for Antibodies to Siltuximab | 3 Participants |
Secondary
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.
Time frame: Up to 6 years
Population: Safety analysis set included all enrolled participants in this study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Siltuximab | Overall Survival | NA years |
Secondary
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.
Time frame: Up to 6 years
Population: Population included subset of safety analysis set who previously responded to siltuximab treatment ie, did not report disease progression while receiving siltuximab in study C0328T03 or CNTO328MCD2001.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Siltuximab | Percentage of Previously Responding Participants Who Maintained Disease Control | 96.5 percentage of participants |
Secondary
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.
Time frame: Up to 6 years
Population: Population included subset of safety analysis set who were previously Siltuximab-naive i.e., received placebo in study CNTO328MCD2001 and never received siltuximab prior to enrollment in this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Siltuximab | Percentage of Siltuximab-naive Participants Who Experienced Disease Control | 100 percentage of participants |