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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 79
- 主要终点
- Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Siltuximab+best supportive care (BSC)
Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.
干预措施: Siltuximab (Drug)
Siltuximab+best supportive care (BSC)
Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.
干预措施: Best Supportive Care (BSC) (Drug)
Placebo+BSC
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.
干预措施: Placebo (Drug)
Placebo+BSC
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.
干预措施: Best Supportive Care (BSC) (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review
时间窗: 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
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).
次要结局
- Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review(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))
- Median Duration of Tumor Response - by Independent Radiology Review(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))
- Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline(From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years))
- Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)(Week 13)
- Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline(From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years))
- Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review(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))
- Percentage of Participants Who Achieved Greater Than or Equal to (>=) 15 Gram Per Liter (g/L) Hemoglobin at Week 13 (Hemoglobin Response Rate)(Week 13)
- 6-year Survival Rate(until 6 years)
- Time to Treatment Failure(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)
- Percentage of Participants Who Discontinued Corticosteroids(From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment (approximately 3 years))
- Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline(From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years))