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

NCT ID: NCT00412321

Last Updated: 2014-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2011-04-30

Brief Summary

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.

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.

Conditions

Lymphoma, Non-Hodgkin; Multiple Myeloma; Giant Lymph Node Hyperplasia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (CNTO 328)

Patients will receive 4 administrations of 3 mg/kg CNTO 328 every 2 weeks till Day 43.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 2 (CNTO 328)

Patients will receive 4 administrations of 6 mg/kg CNTO 328 every 2 weeks till Day 43.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 3 (CNTO 328)

Patients will receive 3 administrations of 12 mg/kg CNTO 328 every 2 weeks till Day 43.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 4 (CNTO 328)

Patients will receive 7 administrations of 6 mg/kg CNTO 328 every week till Day 43.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 5 (CNTO 328)

Patients will receive 4 administrations of 12 mg/kg CNTO 328 every 2 weeks till Day 43.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 6 (CNTO 328)

Patients will receive 3 administrations of 12 mg/kg CNTO 328 every 3 weeks till Day 43.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 7a (CNTO 328)

Patients responding to CNTO 328 treatment will receive 9 mg/kg CNTO 328 every 3 weeks.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Cohort 7b (CNTO 328)

Patients responding to CNTO 328 treatment will receive 12 mg/kg CNTO 328 every 3 weeks as extended administration.

Group Type: EXPERIMENTAL

CNTO 328

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Little Rock, Arkansas, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Box 302, New York, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Philadelphia, Pennsylvania, United States

Houston, Texas, United States

Seattle, Washington, United States

Countries

United States

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=171&filename=CR008566_CSR.pdf

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

Other Identifiers

C0328T03

Identifier Type: OTHER

Identifier Source: secondary_id

CR008566

Identifier Type: -

Identifier Source: org_study_id