Clinical trial NCT01024036: A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease
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 Subjects With Multicentric Castleman's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multicentric Castleman's Disease
Keywords: Multicentric Castleman's Disease
MCD
CNTO 328
Best Supportive Care
Tumor
Symptomatic response
Pharmacokinetics
Interleukin-6
IL6
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2009-12-02
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review
timeFrame: 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:
measure: Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review
timeFrame: 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)
measure: Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review
timeFrame: 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)
measure: Median Duration of Tumor Response - by Independent Radiology Review
timeFrame: 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)
measure: Time to Treatment Failure
timeFrame: 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
measure: Percentage of Participants Who Achieved Greater Than or Equal to (>=) 15 Gram Per Liter (g/L) Hemoglobin at Week 13 (Hemoglobin Response Rate)
timeFrame: Week 13
measure: Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)
timeFrame: Week 13
measure: Percentage of Participants Who Discontinued Corticosteroids
timeFrame: From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment (approximately 3 years)
measure: 6-year Survival Rate
timeFrame: until 6 years
measure: Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline
timeFrame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)
measure: Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline
timeFrame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)
measure: Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline
timeFrame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment (approximately 3 years)
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Tampa
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Lansing
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Chapel Hill
country: United States
state: North Carolina
city: Greenville
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: East Melbourne
country: Australia
city: Brussels
country: Belgium
city: Leuven
country: Belgium
city: Brasilia
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Toronto
country: Canada
city: Beijing
country: China
city: Chengdu
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Shanghai
country: China
city: Cairo
country: Egypt
city: Clermont Ferrand
country: France
city: Grenoble Cedex 1
country: France
city: Lille Cedex
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Rennes
country: France
city: Tours Cedex 9
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Sha Tin
country: Hong Kong
city: Budapest
country: Hungary
city: Hyderabad N/A
country: India
city: Pune
country: India
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Seoul
country: Korea, Republic of
city: Pandan
country: Malaysia
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Oslo
country: Norway
city: Kazan
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: St.-Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Taipei
country: Taiwan
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.