Clinical Trial: A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Subje

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 Summary: 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.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: 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 ]

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).


Original Primary Outcome: Durable tumor and symptomatic response. [ Time Frame: 48 weeks after the last patient begins study treatment. ]

Current Secondary Outcome:

  • 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 ]
    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 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 ]
    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 [ 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 ]
    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).
  • 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 ]
    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 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 ]
    Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).
  • 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 ]
    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).
  • 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 ]
    The FACIT-F, a 13-item ins

    Original Secondary Outcome:

    • Clinical efficacy [ Time Frame: 48 weeks after last patient begins study treatment ]
    • Patient reported outcomes [ Time Frame: 48 weeks after last patient begins study treatment ]
    • Pharmacokinetics (the way the body absorbs, distributes and gets rid of a drug) of CNTO 328 among MCD patients [ Time Frame: 48 weeks after last patient begins study treatment ]
    • Immune response [ Time Frame: 48 weeks after last patient begins study treatment ]


    Information By: Janssen Research & Development, LLC

    Dates:
    Date Received: November 30, 2009
    Date Started: March 2010
    Date Completion: February 2017
    Last Updated: October 5, 2016
    Last Verified: October 2016