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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01024036




Registration number
NCT01024036
Ethics application status
Date submitted
30/11/2009
Date registered
2/12/2009
Date last updated
21/03/2018

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease
Scientific 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
Secondary ID [1] 0 0
CNTO328MCD2001
Secondary ID [2] 0 0
CR016705
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multicentric Castleman's Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Siltuximab
Treatment: Drugs - Placebo
Treatment: Drugs - Best Supportive Care (BSC)

Experimental: Siltuximab+best supportive care (BSC) - Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.

Placebo Comparator: 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.


Treatment: Drugs: Siltuximab
Siltuximab 11 mg/kg will be administered by 1-hour intravenous infusion every 3 weeks

Treatment: Drugs: Placebo
Placebo will be administered by 1-hour intravenous infusion every 3 weeks

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review - 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).
Timepoint [1] 0 0
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
Secondary outcome [1] 0 0
Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review - 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.
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review - 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).
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Median Duration of Tumor Response - by Independent Radiology Review - 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).
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Time to Treatment Failure - 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).
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Percentage of Participants Who Achieved Greater Than or Equal to (>=) 15 Gram Per Liter (g/L) Hemoglobin at Week 13 (Hemoglobin Response Rate) - Hemoglobin response rate is defined as percentage of participants who achieved >= 15 g/L hemoglobin at Week 13.
Timepoint [5] 0 0
Week 13
Secondary outcome [6] 0 0
Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate) - Hemoglobin response rate is defined as percentage of participants who achieved >= 20 g/L hemoglobin at Week 13.
Timepoint [6] 0 0
Week 13
Secondary outcome [7] 0 0
Percentage of Participants Who Discontinued Corticosteroids - Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).
Timepoint [7] 0 0
From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment (approximately 3 years)
Secondary outcome [8] 0 0
6-year Survival Rate - 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.
Timepoint [8] 0 0
until 6 years
Secondary outcome [9] 0 0
Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline - 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).
Timepoint [9] 0 0
From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)
Secondary outcome [10] 0 0
Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline - 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.
Timepoint [10] 0 0
From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)
Secondary outcome [11] 0 0
Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline - 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.
Timepoint [11] 0 0
From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- East Melbourne
Recruitment postcode(s) [1] 0 0
- East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Belgium
State/province [12] 0 0
Brussels
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Brazil
State/province [14] 0 0
Brasilia
Country [15] 0 0
Brazil
State/province [15] 0 0
Porto Alegre
Country [16] 0 0
Brazil
State/province [16] 0 0
Rio De Janeiro
Country [17] 0 0
Brazil
State/province [17] 0 0
Sao Paulo
Country [18] 0 0
Canada
State/province [18] 0 0
Toronto
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Chengdu
Country [21] 0 0
China
State/province [21] 0 0
Guangzhou
Country [22] 0 0
China
State/province [22] 0 0
Hangzhou
Country [23] 0 0
China
State/province [23] 0 0
Shanghai
Country [24] 0 0
Egypt
State/province [24] 0 0
Cairo
Country [25] 0 0
France
State/province [25] 0 0
Clermont Ferrand
Country [26] 0 0
France
State/province [26] 0 0
Grenoble Cedex 1
Country [27] 0 0
France
State/province [27] 0 0
Lille Cedex
Country [28] 0 0
France
State/province [28] 0 0
Montpellier
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Rennes
Country [31] 0 0
France
State/province [31] 0 0
Tours Cedex 9
Country [32] 0 0
France
State/province [32] 0 0
Vandoeuvre Les Nancy
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Mainz
Country [35] 0 0
Germany
State/province [35] 0 0
München
Country [36] 0 0
Hong Kong
State/province [36] 0 0
Sha Tin
Country [37] 0 0
Hungary
State/province [37] 0 0
Budapest
Country [38] 0 0
India
State/province [38] 0 0
Hyderabad N/A
Country [39] 0 0
India
State/province [39] 0 0
Pune
Country [40] 0 0
Israel
State/province [40] 0 0
Petach Tikva
Country [41] 0 0
Israel
State/province [41] 0 0
Ramat Gan
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Seoul
Country [43] 0 0
Malaysia
State/province [43] 0 0
Pandan
Country [44] 0 0
Netherlands
State/province [44] 0 0
Rotterdam
Country [45] 0 0
New Zealand
State/province [45] 0 0
Auckland
Country [46] 0 0
Norway
State/province [46] 0 0
Oslo
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Kazan
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Saint-Petersburg
Country [50] 0 0
Russian Federation
State/province [50] 0 0
St.-Petersburg
Country [51] 0 0
Singapore
State/province [51] 0 0
Singapore
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taipei
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01024036
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications