Health Condition 1: null- Multicentric Castlemans Disease
Conditions
Interventions
Intervention1: CNTO328: Dose will be 11 mg/kg for 1 hour every 3 weeks cycle. 18cycles will be gioven to the patient.
Control Intervention1: parallel placebo controlled trial.: Dose will be 11 mg/kg f
Sponsors
Johnson and Johnson Limited
Eligibility
Inclusion criteria
Inclusion criteria: 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 ¡Ý 1 that are attributable to the disease (see Attachment 1), 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. ¡Ý 18 years of age 3. Pretreatment clinical laboratory values meeting these criteria within 4 weeks before treatment: a. Absolute neutrophil count (ANC) ¡Ý 1.0 x 109/L b. Platelets ¡Ý 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 above 2.5 x ULN, subjects will be eligible if alkaline phosphatase liver fraction is within 2.5 x ULN d. Serum creatinine ¡Ü 3.0 mg/dL 4. ECOG Performance Status of 0, 1, or 2 (see Attachment 2) 5. Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone (or equivalent; see Attachment 3), 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 [¦Â-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.
Exclusion criteria
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 ¡Ý 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 ¦Á (TNF¦Á) 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 allergies, hypersensitivity, or intolerance 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 MCD.Timepoint: Primary Out come will be measured at the end of treatment, lenghtn of treatment is 18 cycles of 3 weeks each. | — |
Secondary
| Measure | Time frame |
|---|---|
| ? 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 hemoglobinTimepoint: 21 day cycle | — |
Countries
Democratic People's Republic of Korea, Egypt, France, Germany, Hungary, India, Netherlands, Norway, Poland, Portugal, Republic of Korea, Spain, Ukraine, United Kingdom, United States of America
Contacts
Public ContactRavinder Tyagi
Johnson and Johnson Limited
Outcome results
None listed