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Study Summary
No. 2009-0608:.......Lymphoma......Luis E. Fayad......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2009-0608
Study 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
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Physician New Patient Referral
Name:Luis E. FayadPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:LymphomaSupported By:Janssen Research & Development, LLC
Phase of Study:Phase IIReturn
Visit:
During cycle 1(Days 1, 8, and 15), participants will visit the doctor 3 times;
off study/end of treatment (30 days after the last does of study drug).
Treatment
Agents:
CNTO 328Home Care:NA
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Treatment is given in cycles. Each cycle is 21 days. Treatment with study drug
(either CNTO or placebo) occurs on the 1st day of each cycle.
Description/
Intervention:
The goal of this clinical research study is to study the effectiveness of CNTO
328 (Siltuximab) and best supportive care (BSC), compared to BSC alone, in
patients with MCD. The safety of CNTO 328 and its ability to control symptoms
of the disease will also be studied.
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Study Objectives / Outcomes
    Primary Objective
    The primary objective of this study is to demonstrate that CNTO 328 (Anti-IL-6 Monoclonal Antibody) in combination with Best Supportive Care (BSC) is superior to BSC in terms of durable tumor and symptomatic response among subjects with multicentric Castleman's disease (MCD).

    Secondary Objectives
    The secondary objectives of this study are:
    1) 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)
    2) To study the safety of prolonged dosing;
    3) To determine the pharmacokinetics of CNTO 328 among subjects with MCD; and
    4) To determine a baseline hepcidin value predictive of a >/= 2 g/dL increase in hemoglobin.

    Exploratory Objectives
    Exploratory objectives, which are not part of the primary reporting effort, are:
    1) To identify potential pharmacodynamic biomarkers of response for IL-6-driven neoplasia; and
    2) To correlate pharmacodynamic biomarkers with indicators of clinical efficacy.
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Study Status Information
Study Activation / Registration Date:09/09/2010
IRB Review and Approval Date:09/09/2010
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:78
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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 or by marked laboratory abnormalities 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 be limited to cutaneous lesions. Elevations in acute-phase proteins (CRP, fibrinogen) and increased ESR in the absence of other 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 10^9/L; b. Platelets >/= 75 x 10^9/L;c. ALT; 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; total bilirubin 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 randomization

6) Women of childbearing potential must agree to use adequate birth control measures during the study and for 3 months after receiving the last dose of study agent, and must have a negative pregnancy test (serum or urine beta-human chorionic gonadotropin [Beta-HCG]) at screening. Men must agree to use adequate birth control measures and to not donate sperm during the study and for 3 months after receiving the last dose of study agent.

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.

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 alpha (TNF-alpha) antibodies, immunosuppressive agents (except stable doses of corticosteroids), and erythropoietin stimulating agents (ESAs).

8) Received an investigational drug (including vaccines), erythropoietin stimulating agents (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.

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Links
Registration Number: NCT01024036
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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