Clinical Trial: A Safety and Efficacy Study of CNTO 328 in Patients With B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1 Study of Multiple Intravenous Administrations of a Chimeric Antibody Against Interleukin-6 (CNTO 328) in Subjects With B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or

  • Number of Patients With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 3 years after the last administration of study medication ]
    Number of Patients with adverse events will be reported.
  • Serum Concentration of CNTO 328 [ Time Frame: Up to Day 71 ]
    Serum Concentration of CNTO 328 will be reported.


    • Original Primary Outcome: Assess the safety and pharmacokinetics of multiple dosing regimens of CNTO 328 administered as an intravenous (IV) infusion in patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, or Castleman's Disease at Day 71.

    Current Secondary Outcome:

    • Pharmacodynamics of CNTO 328 [ Time Frame: Up to Day 71 ]
      Pharmacodynamic parameters C-reactive protein, interleukin-6 (IL-6), soluble IL-6 receptor [GP80], soluble GP130, TNFα, ΙL-8, IL-10, soluble IL-2 receptor (sIL-2R), IFNγ, serum amyloid A (SAA), N-telopeptide (NTx), C-telopeptide (CTx), hepcidin-25, VEGF, and fibroblast growth factor will be assessed.
    • Plasma antibodies to CNTO 328 [ Time Frame: Up to Week 24 ]
      Plasma antibodies to CNTO 328 will be used to evaluate the immunogenicity of CNTO 328.
    • Number of participants with Castleman's disease who achieved tumor response [ Time Frame: Screening phase (4 weeks before administration of study medication), Day 36, and Day 57 ]
      Evaluation of tumor response for subjects with Castleman's disease were performed by central review according to the standard criteria, developed by an NCI-sponsored international working group (Cheson et al, 1999).
    • Number of participants with multiple myeloma who achieved disease response [ Time Frame: Screening phase (4 weeks before administration of study medication), Day 36, and Day 57 ]
      Evaluation of disease response for subjects with Multiple Myeloma were performed by the investigators according to the response criteria developed by an international group of multiple myeloma and bone marrow transplant experts (Blade et al, 1998).
    • Number of participants with B-cell non-Hodgkin's lymphoma and multiple myeloma who achieved clinical benefit (CB) [ Time Frame: Up to Day 71 ]
      CB will assess pain (by Pain intensity [PI] and 7-items assessing how much pain interfered with daily activities), performance status (by Karnofsky performance status which quantifies participant's well-being and activities of daily life), and weight change. PI score will be assessed by 4 questions (Q) rated on 11-point numerical rating scale ranging from "0=no pain" to "10=higher severity of pain". Each participant will be classified as either CB responder (i.e., if +ve for at least 1 of 3 primary CB measures and stable for other 2) or Non-responder (If a participant is stable on all 3 primary measures OR if -ve for any 1 of 3 primary measures).
    • Number of participants with Castleman's disease who achieved clinical benefit [ Time Frame: Up to Day 71 ]
      CB assessments for participant with Castleman's disease consist of the following 6 measures: hemoglobin, fatigue, anorexia, fever, weight, and size of largest lymph node. Each participant will be classified as either improved, stable, or worsening for each of the measures. If a participant has improved for at least 1 of the 6 measures and is at least stable for the remaining measures, participant will be considered to be a responder for CB. If a participant has worsening for at least 1 of the 6 measures, participant will be considered as having progression for CB. Any other participant will be considered to be stable for CB. Any "improved" or "stable" assessment of the lymph node parameter for CB must be confirmed by radiographic imaging. If a participant shows progression for CB at 2 consecutive assessments the participant must discontinue study treatment.
    • Number of participants with B-cell non-Hodgkin's lymphoma who achieved disease response [ Time Frame: Screening phase (4 weeks before administration of study medication), Day 36, and Day 57 ]
      Evaluation of disease response for subjects with B-cell non-Hodgkin's lymphoma were performed by the investigators according to the standard criteria, developed by an NCI-sponsored international working group (Cheson et al, 1999).


    Original Secondary Outcome: Assess the pharmacodynamics, immune response, and clinical effects of multiple dosing regimens of CNTO 328 administered as an IV infusion in patients with B cell non-Hodgkin's lymphoma, multiple myeloma or Caslteman's Disease at Day 71.

    Information By: Centocor, Inc.

    Dates:
    Date Received: December 15, 2006
    Date Started: May 2005
    Date Completion:
    Last Updated: June 30, 2014
    Last Verified: June 2014