A Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Patients With Multicentric Castleman's Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01400503
First received: April 21, 2011
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the long-term safety of siltuximab in patients with multicentric Castleman's disease (MCD).


Condition Intervention Phase
Multicentric Castleman's Disease
Drug: Siltuximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Subjects With Multicentric Castleman's Disease

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of Patients with Adverse Events [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.


Secondary Outcome Measures:
  • Number of multicentric Castleman's disease patients evaluated for assessment of atypical IL-6 splice variants or cleavage fragments [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Pharmacodynamic biomarker evaluations include assessment of atypical IL-6 splice variants or cleavage fragments.

  • Number of multicentric Castleman's disease patients evaluated for assessment of C-reactive protein [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Pharmacodynamic biomarker evaluations include assessment of C-reactive protein.

  • Number of previously responding multicentric Castleman's disease patients and siltuximab-naive patients who maintain disease control [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.

  • Duration of multicentric Castleman's disease control [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.

  • Duration of survival for patients with multicentric Castleman's disease [ Time Frame: From randomization up to death, lost to follow-up or withdrawal of consent, whichever come first; until 6 years ] [ Designated as safety issue: No ]
    Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.

  • Multicentric Castleman's Disease Symptom Scale scores [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Multicentric Castleman's Disease Symptom Scale scores questionnaire will only be completed by the sub-population from the C0328T03 study. These scores will be calculated as a measure of severity of symptoms.

  • Assessment of glycoform clearance analysis [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
    For evaluating the clearance and degradation of glycoforms after administration of siltuximab, 6 serum samples will be collected from 5 former C0328T03 patients (a limited number of samples are needed for this analysis).

  • Assessment of in vivo protein degradation analysis [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
    Siltuximab will be isolated from the serum samples using an anti-Id antibody. The purified protein will be analyzed by liquid chromatography/mass spectroscopy techniques (intact mass and peptide mapping).


Enrollment: 60
Study Start Date: April 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Siltuximab
Siltuximab 11 mg/kg, intravenous infusion, given as a 1-hour infusion every 3 weeks.
Drug: Siltuximab
Type=exact number, unit=mg/kg, number=11, form=intravenous solution, route=intravenous. Siltuximab given as a 1-hour infusion every 3 weeks.

Detailed Description:

This is an open-label (all people know the identity of the intervention), multicenter (study conducted in multiple sites), non-randomized (patients are not assigned by chance to treatment groups), Phase 2b study. Up to 75 patients with MCD will be eligible for the study, the majority of whom will be on active therapy with siltuximab at the time of enrollment. Patients will be either siltuximab-naive or have not progressed on siltuximab in the opinion of the investigator. Duration of disease control and survival will be assessed. Data collection for patients who discontinue treatment will be limited to survival, occurrence of malignancies, and subsequent therapies for MCD, which will be assessed twice per year until the patient has been lost to follow up or has withdrawn consent for the study, whichever occurs first. An interim analysis will be conducted (no later than 2 years after the start of enrollment) to further evaluate the benefit and safety of long-term treatment with siltuximab in patients with MCD. A data will occur at 6 years after the start of enrollment and for those patients remaining on treatment after the data cutoff, data collection will be limited to pregnancies and serious adverse events (SAEs), including information on study agent administration and concomitant medications associated with an SAE. Safety evaluations for adverse events, clinical laboratory tests, vital signs, and physical examination will be performed throughout the study. The end of study is the date of the last assessment for the last patient.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has multicentric Castleman's disease
  • Have previously been enrolled in Study C0328T03 or CNTO328MCD2001 (either treatment arm)
  • Have had their last administration of study treatment (siltuximab or placebo) less than 6 weeks (window of plus 2 weeks) prior to first dose
  • Patients must not have had disease progression while receiving siltuximab. For those patients originally assigned to placebo in the CNTO328MCD2001 study, patients who have received less than 4 months of siltuximab following crossover will also be eligible
  • Have adequate clinical laboratory parameters within 2 weeks prior to the first dose of siltuximab for this study

Exclusion Criteria:

  • Unmanageable toxicity, an adverse event, progression of disease, or withdrawal of consent as reason for discontinuing treatment from previous sponsor-initiated siltuximab study
  • Vaccination with live, attenuated vaccines within 4 weeks of first dose of this study
  • Known unmanageable allergies, hypersensitivity, intolerance to monoclonal antibodies, to murine, chimeric, human proteins or their excipients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01400503

  Show 26 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01400503     History of Changes
Other Study ID Numbers: CR018469, CNTO328MCD2002, 2010-022837-27
Study First Received: April 21, 2011
Last Updated: May 26, 2014
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines
Germany: Ethics Commission
Canada: Health Canada

Keywords provided by Janssen Research & Development, LLC:
Multicentric Castleman's Disease
Multicentric
Castleman
Siltuximab
Long term safety

Additional relevant MeSH terms:
Giant Lymph Node Hyperplasia
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014