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

NCT01024036 | Completed Phase 2 Results DMC

• 3 other identifiers: CR016705CNTO328MCD20012009-012380-34
• Study Type: interventional
• Target: 79
• Locations: 23 countries
• Sites: 56

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.

Conditions

Multicentric Castleman's Disease

Keywords

Multicentric Castleman's Disease; MCD; CNTO 328; Best Supportive Care; Tumor; Symptomatic response; Pharmacokinetics; Interleukin-6; IL6

Outcome Measures

Primary Outcomes (1)

• 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).

  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 Outcomes (11)

• 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)

• 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)

• 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)

• 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

• 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

Study Arms (2)

Siltuximab+best supportive care (BSC)

EXPERIMENTAL

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

Drug: Siltuximab; Drug: Best Supportive Care (BSC)

Placebo+BSC

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Best Supportive Care (BSC)

Interventions

Siltuximab DRUG

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

Also known as: CNTO 328

Siltuximab+best supportive care (BSC)

Placebo DRUG

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

Placebo+BSC

Best Supportive Care (BSC) DRUG

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

Placebo+BSC; Siltuximab+best supportive care (BSC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (56)

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Little Rock, Arkansas, United States

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Los Angeles, California, United States

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Tampa, Florida, United States

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Boston, Massachusetts, United States

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Lansing, Michigan, United States

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Rochester, Minnesota, United States

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Chapel Hill, North Carolina, United States

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Greenville, South Carolina, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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East Melbourne, Australia

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Brussels, Belgium

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Leuven, Belgium

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Brasília, Brazil

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Porto Alegre, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Toronto, Canada

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Beijing, China

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Chengdu, China

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Guangzhou, China

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Hangzhou, China

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Shanghai, China

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Cairo, Egypt

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Clermont-Ferrand, France

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Grenoble, France

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Lille, France

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Montpellier, France

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Paris, France

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Rennes, France

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Tours, France

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Vandœuvre-lès-Nancy, France

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Berlin, Germany

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Mainz, Germany

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München, Germany

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Shatin, Hong Kong

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Budapest, Hungary

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Hyderabad, India

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Pune, India

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Petah Tikva, Israel

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Ramat Gan, Israel

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Pandan, Malaysia

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Rotterdam, Netherlands

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Auckland, New Zealand

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Oslo, Norway

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Kazan', Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Singapore, Singapore

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Seoul, South Korea

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Barcelona, Spain

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Madrid, Spain

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Taipei, Taiwan

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London, United Kingdom

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Manchester, United Kingdom

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Related Publications (3)

• 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.

  PMID: 35793409 DERIVED

• 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.

  PMID: 28087540 DERIVED

• 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.

  PMID: 25042199 DERIVED

MeSH Terms

Conditions

Multi-centric Castleman's Disease; Macular dystrophy, corneal type 1; Neoplasms

Interventions

siltuximab

Results Point of Contact

• Title: DIRECTOR CLINICAL RESEARCH
• Organization: Janssen R&D US

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2009
• First Posted: December 2, 2009
• Study Start: March 18, 2010
• Primary Completion: March 25, 2013
• Study Completion: February 24, 2017
• Last Updated: March 21, 2018
• Results First Posted: August 20, 2014

Record last verified: 2018-02

Locations

NZ (1); SG (1); AU (1); KR (1); TW (1); NO (1); GB (2); EG (1); IN (2); ES (2); MY (1); BR (4); RU (3); HU (1); IL (2); DE (3); FR (8); HK (1); CA (1); US (11); BE (2); NL (1); CN (5)