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

NCT ID: NCT01024036

Last Updated: 2018-03-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

79 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-18

Study Completion Date

2017-02-24

Brief Summary

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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

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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.

Conditions

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Multicentric Castleman's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Siltuximab+best supportive care (BSC)

Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.

Group Type EXPERIMENTAL

Siltuximab

Intervention Type DRUG

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

Best Supportive Care (BSC)

Intervention Type DRUG

BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Best Supportive Care (BSC)

Intervention Type DRUG

BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.

Interventions

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Siltuximab

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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CNTO 328

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Little Rock, Arkansas, United States

Site Status

Los Angeles, California, United States

Site Status

Tampa, Florida, United States

Site Status

Boston, Massachusetts, United States

Site Status

Lansing, Michigan, United States

Site Status

Rochester, Minnesota, United States

Site Status

Chapel Hill, North Carolina, United States

Site Status

Greenville, South Carolina, United States

Site Status

Houston, Texas, United States

Site Status

Salt Lake City, Utah, United States

Site Status

Seattle, Washington, United States

Site Status

East Melbourne, , Australia

Site Status

Brussels, , Belgium

Site Status

Leuven, , Belgium

Site Status

Brasília, , Brazil

Site Status

Porto Alegre, , Brazil

Site Status

Rio de Janeiro, , Brazil

Site Status

São Paulo, , Brazil

Site Status

Toronto, , Canada

Site Status

Beijing, , China

Site Status

Chengdu, , China

Site Status

Guangzhou, , China

Site Status

Hangzhou, , China

Site Status

Shanghai, , China

Site Status

Cairo, , Egypt

Site Status

Clermont-Ferrand, , France

Site Status

Grenoble, , France

Site Status

Lille, , France

Site Status

Montpellier, , France

Site Status

Paris, , France

Site Status

Rennes, , France

Site Status

Tours, , France

Site Status

Vandœuvre-lès-Nancy, , France

Site Status

Berlin, , Germany

Site Status

Mainz, , Germany

Site Status

München, , Germany

Site Status

Shatin, , Hong Kong

Site Status

Budapest, , Hungary

Site Status

Hyderabad, , India

Site Status

Pune, , India

Site Status

Petah Tikva, , Israel

Site Status

Ramat Gan, , Israel

Site Status

Pandan, , Malaysia

Site Status

Rotterdam, , Netherlands

Site Status

Auckland, , New Zealand

Site Status

Oslo, , Norway

Site Status

Kazan', , Russia

Site Status

Moscow, , Russia

Site Status

Saint Petersburg, , Russia

Site Status

Singapore, , Singapore

Site Status

Seoul, , South Korea

Site Status

Barcelona, , Spain

Site Status

Madrid, , Spain

Site Status

Taipei, , Taiwan

Site Status

London, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Belgium Brazil Canada China Egypt France Germany Hong Kong Hungary India Israel Malaysia Netherlands New Zealand Norway Russia Singapore South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 35793409 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28087540 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25042199 (View on PubMed)

Other Identifiers

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CNTO328MCD2001

Identifier Type: OTHER

Identifier Source: secondary_id

2009-012380-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR016705

Identifier Type: -

Identifier Source: org_study_id

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