Trial record 2 of 16 for:    "Angiofollicular lymph hyperplasia"

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00412321
First received: December 15, 2006
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to evaluate of the study of different CNTO 328 doses and schedules and to see if CNTO 328 has any effect on Non-hodgkin's Lymphoma, Multiple Myeloma or Castleman's disease.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Multiple Myeloma
Giant Lymph Node Hyperplasia
Drug: CNTO 328
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Castleman's Disease

Resource links provided by NLM:


Further study details as provided by Centocor, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Number of Patients with adverse events will be reported.

  • Serum Concentration of CNTO 328 [ Time Frame: Up to Day 71 ] [ Designated as safety issue: No ]
    Serum Concentration of CNTO 328 will be reported.


Secondary Outcome Measures:
  • Pharmacodynamics of CNTO 328 [ Time Frame: Up to Day 71 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 67
Study Start Date: May 2005
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (CNTO 328)
Patients will receive 4 administrations of 3 mg/kg CNTO 328 every 2 weeks till Day 43.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 2 (CNTO 328)
Patients will receive 4 administrations of 6 mg/kg CNTO 328 every 2 weeks till Day 43.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 3 (CNTO 328)
Patients will receive 3 administrations of 12 mg/kg CNTO 328 every 2 weeks till Day 43.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 4 (CNTO 328)
Patients will receive 7 administrations of 6 mg/kg CNTO 328 every week till Day 43.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 5 (CNTO 328)
Patients will receive 4 administrations of 12 mg/kg CNTO 328 every 2 weeks till Day 43.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 6 (CNTO 328)
Patients will receive 3 administrations of 12 mg/kg CNTO 328 every 3 weeks till Day 43.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 7a (CNTO 328)
Patients responding to CNTO 328 treatment will receive 9 mg/kg CNTO 328 every 3 weeks.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.
Experimental: Cohort 7b (CNTO 328)
Patients responding to CNTO 328 treatment will receive 12 mg/kg CNTO 328 every 3 weeks as extended administration.
Drug: CNTO 328
Patients will receive administrations of CNTO 328 with dose ranging from 3 mg/kg to 12 mg/kg weekly, every 2 or 3 weeks till Day 43 in cohorts 1 to 6. After cohort 6, if the clinical response is found to be suboptimal, the patients will receive 9 mg/kg or 12 mg/kg every 3 weeks in cohorts 7a. Participants in Cohort 7a who will experience intolerable toxicity after escalating to or receiving 12 mg/kg every 3 weeks will have the option of reverting to a dose of 9 mg/kg every 3 weeks if the investigator felt it was clinically indicated. In cohort 7b participants will receive 12 mg/kg CNTO 328 every 3 weeks.

Detailed Description:

This research study will use a type of drug called anti-IL-6 antibody, also known as CNTO 328. An antibody is a substance in the body that fights infection. CNTO 328 is an investigational drug that has been shown to slow down tumor growth or shrink tumors when tested in animals. In a previous clinical trial in patients with multiple myeloma (blood cancer), CNTO 328 appeared to be a potent inhibitor of IL-6 . One study has been completed for kidney cancer. There are studies ongoing in humans with multiple myeloma and prostate cancer to see if CNTO 328 is safe and to see what effects it has on these types of cancer. This is an open-label, nonrandomized, dose-finding phase 1 study with CNTO 328 in patients with B- cell non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's disease. The purpose of this study is to evaluate different doses and schedules of CNTO 328 to see which dose/schedule is safe. CNTO 328 will be given through a small tube that goes directly into your vein, called an intravenous (IV) infusion. Depending on when the patient enters the study, the patient will be assigned to receive one course of CNTO 328 in one of the following groups: Group 1: 3 mg/kg 2 hr IV infusion every 2 weeks for 4 doses. Group 2: 6 mg/kg 2 hr IV infusion every 2 weeks for 4 doses. Group 3: 12 mg/kg 2 hr IV infusion every 3 weeks for 3 doses. Group 4: 6 mg/kg 2 hr IV infusion every week for 7 doses. Group 5: 12 mg/kg 2 hr IV infusion every 2 weeks for 4 doses. Group 6: 12 mg/kg 1 hr IV infusion every 3 weeks for 3 doses. Group 7a: 9 mg/kg 1 hr IV infusion every 3 weeks. Group 7b: 12 mg/kg 1hr IV infusion every 3 weeks for Castleman's patients only. In Groups 1-5, the overall amount of study drug that will be given increases with each higher group. Group 1 will be filled before Group 2 starts and Group 2 will be filled before Group 3 starts, etc. In this way, CNTO 328 can be tested more safely. Both the patient and the study doctor will know to which group the patient is assigned. Patients will remain in the group that they are assigned to for the entire time of participation in the study. Up to 70 patients may take part in this study. Patients in Groups 1-6 will be in the study for up to 34 weeks prior to Post Study Follow-Up. Screening: up to 4 weeks before the first dose schedule of CNTO 328. Treatment: up to 6 weeks of treatment with CNTO 328. Extended Dosing: Patients assigned to Groups 1-6, and their cancer or disease has become stable or better while receiving CNTO 328, may be able to receive additional courses of study drug. Patients in Group 7 will be in the study until their disease gets worse, they can no longer tolerate CNTO 328, the study doctor feels it is in their best interest to stop CNTO 328 or they longer wish to participate in the study. Long Term Follow-Up: Patients will be contacted by telephone every six months after the last infusion of study drug to assess the patient's disease status and survival. Dose (6-12 mg/kg) and frequency (weekly or 2 or 3 week intervals) of dosing depends upon Group assignment. CNTO 328 will be given through a small tube that goes directly into your vein, called an intravenous (IV) infusion. The infusion will take about 2 hours to complete for groups 1-5 and 1 hour for Groups 6 and 7. In Groups 1-6, CNTO 328 will be given once every 1, 2 or 3 weeks from days 1 to 43 depending on treatment assignment. In Group 7a and Group 7b, CNTO 328 will be given on day 1 of each 21 day cycle.

  Eligibility

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

Inclusion Criteria:

  • Diagnosed with B-cell non-Hodgkin's lymphoma, multiple myeloma, or Castleman's Disease which has progressed on or after standard therapy or for which there is no effective standard therapy, or which is not suitable for standard therapy
  • Detectable serum C-Reactive Protein
  • At least 4 weeks since prior systemic therapy, radiotherapy, or surgery
  • Must meet protocol lab criteria (adequate bone marrow, liver and renal function) to be assessed at patient's first visit to the study center

Exclusion Criteria:

  • Received any investigational drug within 30 days or 5 half-lives of the investigational drug, whichever is longer
  • History of receiving murine or human-murine recombination products, such as G250, BE-8, and other monoclonal antibodies. (Note: Prior rituximab treatment is not an exclusion criterion)
  • Serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease or congestive heart failure
  • Known human immunodeficiency virus seropositivity, acquired immunodeficiency syndome, hepatitis C or active hepatitis B infection. For Cohort 7, known human herpesvirus-8 seropositivity
  • Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or an allogeneic peripheral blood stem cell transplant
  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: NCT00412321

Locations
United States, Arkansas
Little Rock, Arkansas, United States
United States, Florida
Tampa, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, New York
Box 302, New York, United States
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
United States, Washington
Seattle, Washington, United States
Sponsors and Collaborators
Centocor, Inc.
Investigators
Study Director: Centocor, Inc. Clinical Trial Centocor, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00412321     History of Changes
Other Study ID Numbers: CR008566, C0328T03
Study First Received: December 15, 2006
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor, Inc.:
Lymphoma, Non-Hodgkin
Multiple Myeloma
Castleman's disease
intravenous
IL-6

Additional relevant MeSH terms:
Giant Lymph Node Hyperplasia
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Lymphoma
Hyperplasia
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 18, 2014