Overview

This trial is active, not recruiting.

Condition multicentric castleman's disease
Treatments siltuximab, placebo, best supportive care (bsc)
Phase phase 2
Sponsor Janssen Research & Development, LLC
Start date March 2010
End date March 2013
Trial size 79 participants
Trial identifier NCT01024036, 2009-012380-34, CNTO328MCD2001, CR016705

Summary

The purpose of this study is to demonstrate that CNTO 328 when administered in combination with best supportive care (BSC) is superior to BSC in terms of durable tumor and symptomatic response (complete response or partial response) among patients with Multicentric Castleman's Disease.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.
siltuximab CNTO 328
Siltuximab 11 mg/kg will be administered by 1-hour intravenous infusion every 3 weeks
best supportive care (bsc)
BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.
(Placebo Comparator)
Placebo will be administered as a 1-hour intravenous infusion every 3 weeks + BSC. Participants who do not respond to placebo during the blinded treatment period will have option to crossover and receive siltuximab 11 mg/kg which will be administered by 1-hour intravenous infusion every 3 weeks + BSC during the unblinded treatment period.
placebo
Placebo will be administered by 1-hour intravenous infusion every 3 weeks
best supportive care (bsc)
BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.

Primary Outcomes

Measure
Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review
time frame: From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from the study, or up to 48 weeks after the last participant started study medication, whichever occurred earlier

Secondary Outcomes

Measure
Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review
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
Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review
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
Median Duration of Tumor Response - by Independent Radiology Review
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
Time to Treatment Failure
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, whichever occurred earlier
Percentage of Participants Who Achieved >= 15 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)
time frame: Week 13
Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)
time frame: Week 13
Percentage of Participants Who Discontinued Corticosteroids
time frame: From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment
1-year Survival Rate
time frame: 1 year
Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline
time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment
Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline
time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment
Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline
time frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Measurable and symptomatic Multicentric Castleman's Disease - Adequate organ function as assessed by laboratory values evaluated by the investigator to determine eligibility prior to treatment - Eastern Cooperative Oncology Group performance status of 0, 1, or 2 - Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone, and has remained stable or decreased over the 4 weeks before treatment Exclusion Criteria: - Human Immunodeficiency Virus or Human Herpes Virus-8 positive - Skin lesions as sole measurable manifestation of Multicentric Castleman's Disease - Previous history of lymphoma - Malignancies, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or cancer other than lymphoma, from which the patient has been disease-free for 3 or more years - Concurrent medical condition or disease that may interfere with study participation - Prior exposure to Interleukin-6 or Interleukin-6 receptor targeted therapies

Additional Information

Official title A Randomized, Double Blind, Placebo Controlled Study to Assess the Efficacy and Safety of CNTO 328 (Anti IL 6 Monoclonal Antibody) Plus Best Supportive Care Compared With Best Supportive Care in Subjects With Multicentric Castleman's Disease
Description 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 (blinded and unblinded), and the follow up phase. In the blinded treatment phase, approximately 78 patients will be randomly assigned in 1:2 ratios to either of 2 treatment groups, ie, Placebo + BSC, or CNTO 328 + BSC. Participants receiving placebo + BSC during blinded treatment period who do not respond and have treatment failure will have the option to crossover and receive siltuximab + BSC during unbllinded treatent period. 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Janssen Research & Development, LLC.