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

• Register: EUCTR
• Last refreshed on: 11 September 2012
• Main ID: EUCTR2009-012380-34-HU
• Date of registration: 15/12/2009
• Prospective Registration: Yes
• Primary sponsor: Janssen Biologics BV
• Public 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
• 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
• Date of first enrolment: 18/03/2010
• Target sample size: 78
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012380-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, France, Germany, Hungary, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Measurable and symptomatic MCD proven by biopsy and confirmed by central pathology review. Symptomatic disease is defined clinically by the presence of symptoms with NCI-CTCAE grading = 1 that are attributable to the disease, and for which treatment is indicated. Subjects are required to have measurable disease, which may not be limited to cutaneous lesions. Laboratory abnormalities (eg, elevations in acute-phase proteins [CRP, fibrinogen] and increased ESR) in the absence of clinical symptoms do not qualify as symptomatic disease.
2. = 18 years of age
3. Pretreatment clinical laboratory values meeting these criteria within 4 weeks before treatment:
a. Absolute neutrophil count (ANC) = 1.0 x 109/L
b. Platelets = 75 x 109/L
c. ALT within 2.5 x ULN; total bilirubin within 2.5 x ULN; unfractionated alkaline phosphatase within 2.5 x ULN; if unfractionated alkaline phosphatase is above 2.5 x ULN, subjects will be eligible if alkaline phosphatase liver fraction is within 2.5 x ULN
d. Serum creatinine = 3.0 mg/dL
4. ECOG Performance Status of 0, 1, or 2
5. Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone (or equivalent) and has remained stable or decreased over the 4 weeks before
enrollment
6. Subjects of childbearing potential must use adequate birth control measures.
Negative pregnancy test (serum or urine beta human chorionic gonadotropin
[ß-HCG]) at screening (applicable to women of childbearing potential).
7. Subjects (or their legally-acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Informed consent must be obtained before performing any study-specific procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. HIV or HHV-8 positive
2. Skin lesions as sole measurable manifestation of MCD
3. Previous lymphoma
4. 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 subject has been disease-free for = 3 years.
5. Concurrent medical condition or disease (eg, autoimmune disease, active systemic
infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is
likely to interfere with study procedures or results, or that in the opinion of the
investigator would constitute a hazard for participating in this study
6. Prior exposure to agents targeting IL 6 or the IL 6 receptor
7. Use of disallowed therapies: other concomitant anti-tumor therapies for Castleman’s disease (eg, anti-CD20 antibodies, IL-6- or IL-6 receptor-targeted therapies, chemotherapy), biologic treatments such as anti-tumor necrosis factor a (TNFa) antibodies, immunosuppressive agents (except stable doses of corticosteroids), and erythropoietin stimulating agents (ESAs)
8. Received an investigational drug (including vaccines), ESAs, or any systemic
treatment for Castleman’s disease within 4 weeks (or in the case of rituximab, within
8 weeks) before the planned start of treatment
9. Major surgery within 4 weeks of treatment
10. History of uncontrolled heart disease such as unstable angina, congestive heart
failure, myocardial infarction within preceding 12 months, hemodynamic instability
or known left ventricular ejection fraction (LVEF) < 30%, or clinically significant
rhythm or conduction abnormality
11. Clinically significant infections, including known hepatitis C infection or known to be hepatitis B surface antigen (HBsAg) positive
12. History of allogeneic transplant (except corneal transplants)
13. Known, unmanageable severe infusion related reactions to monoclonal antibodies or to murine, chimeric, or human proteins or their excipients
14. Pregnant or nursing
15. Vaccination with live, attenuated vaccines within 4 weeks of first administration of
study agent
16. Paraneoplastic pemphigus or bronchiolitis obliterans
17. Any condition that, in the opinion of the investigator, would compromise the wellbeing of the subject or the study or prevent the subject from meeting or performing study requirements


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multicentric Castleman's disease
MedDRA version: 13.1 Level: PT Classification code 10050251 Term: Castleman's disease System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: CNTO328
Product Code: CNTO328
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: CNTO 328
Other descriptive name: Chimeric murine human anti-IL-6 monoclonal antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate that CNTO 328 in combination with BSC is superior to BSC in terms of durable tumor and symptomatic response among subjects with multicentric Castleman’s disease (MCD).

Primary end point(s): The primary efficacy endpoint will be durable tumor and symptomatic response. For definitions, see Section 9.2.2 of the protocol.

Secondary Objective: The secondary objectives of this study are:
• To demonstrate additional measures of efficacy (tumor response; duration of response; time to treatment failure; change in hemoglobin levels; ability to discontinue corticosteroids; and improvement in fatigue, physical function, and other disease-related symptoms)
• To study the safety of prolonged dosing
• To determine the pharmacokinetics of CNTO 328 among subjects with MCD
• To determine a baseline hepcidin value predictive of a = 2 g/dL increase in hemoglobin

Secondary ID(s)

CNTO328MCD2001

2009-012380-34-GB