A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease
- Conditions
- Multicentric Castleman's Disease
- Interventions
- Registration Number
- NCT01024036
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 79
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Siltuximab+best supportive care (BSC) Best Supportive Care (BSC) Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC. Placebo+BSC Placebo 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+BSC Best Supportive Care (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. Siltuximab+best supportive care (BSC) Siltuximab Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review 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).
- Secondary Outcome Measures
Name Time Method 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) 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).
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) 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).
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) 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).
Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate) Week 13 Hemoglobin response rate is defined as percentage of participants who achieved \>= 20 g/L hemoglobin at 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) 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.
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) 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.
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 Hemoglobin response rate is defined as percentage of participants who achieved \>= 15 g/L hemoglobin at Week 13.
6-year Survival Rate until 6 years 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 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 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).
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) Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).
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) 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.