Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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
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
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
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)
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)
Timepoint [6] 0 0
Week 13
Secondary outcome [7] 0 0
Percentage of Participants Who Discontinued Corticosteroids
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
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
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
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
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
Sex
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
18/03/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/02/2017
Sample size
Target
Accrual to date
Final
79
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/study/NCT01024036
Trial related presentations / publications
van Rhee F, Rosenthal A, Kanhai K, Martin R, Nishimura K, Hoering A, Fajgenbaum DC. Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. 2022 Aug 23;6(16):4773-4781. doi: 10.1182/bloodadvances.2022007112.
Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, Simpson D, Liu AY, Menke D, Chandrakasan S, Lechowicz MJ, Wong RS, Pierson S, Paessler M, Rossi JF, Ide M, Ruth J, Croglio M, Suarez A, Krymskaya V, Chadburn A, Colleoni G, Nasta S, Jayanthan R, Nabel CS, Casper C, Dispenzieri A, Fossa A, Kelleher D, Kurzrock R, Voorhees P, Dogan A, Yoshizaki K, van Rhee F, Oksenhendler E, Jaffe ES, Elenitoba-Johnson KS, Lim MS. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017 Mar 23;129(12):1646-1657. doi: 10.1182/blood-2016-10-746933. Epub 2017 Jan 13.
van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fossa A, Simpson D, Capra M, Liu T, Hsieh RK, Goh YT, Zhu J, Cho SG, Ren H, Cavet J, Bandekar R, Rothman M, Puchalski TA, Reddy M, van de Velde H, Vermeulen J, Casper C. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014 Aug;15(9):966-74. doi: 10.1016/S1470-2045(14)70319-5. Epub 2014 Jul 17. Erratum In: Lancet Oncol. 2014 Sep;15(10):417.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01024036