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

June 30, 2014 updated by: Centocor, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
67

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States
    • Florida
      • Tampa, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
    • New York
      • Box 302, New York, United States
      • New York, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Texas
      • Houston, Texas, United States
    • Washington
      • Seattle, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 3 years after the last administration of study medication
Serum Concentration of CNTO 328
Time Frame: Up to Day 71
Serum Concentration of CNTO 328 will be reported.
Up to Day 71

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Up to Day 71
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.
Up to Week 24
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).
Screening phase (4 weeks before administration of study medication), Day 36, and Day 57
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).
Screening phase (4 weeks before administration of study medication), Day 36, and Day 57
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).
Up to Day 71
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.
Up to Day 71
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).
Screening phase (4 weeks before administration of study medication), Day 36, and Day 57

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centocor, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 15, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 15, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 1, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR008566
  • C0328T03 (Other Identifier: Centocor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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