A Study Evaluating the Effects of Siltuximab on the Heart in Patients With Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Indolent Multiple Myeloma

January 16, 2015 updated by: Janssen Research & Development, LLC

A Study of Siltuximab (Anti-IL-6 Monoclonal Antibody) Effects on the QT Interval in Subjects With Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Indolent Multiple Myeloma

The purpose of this study is to determine if siltuximab has an effect on the heart function measured by ECG recordings and more specifically to determine if siltuximab has an effect on the QT interval in patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM) or Indolent Multiple Myeloma (IMM). The study will also look to see if siltuximab may be useful in treating patients with MGUS, SMM or IMM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a research study with an experimental drug called siltuximab (also known as CNTO 328). Currently there are studies with siltuximab, completed or ongoing, in patients with blood cancers such as multiple myeloma and Castleman's disease and with solid tumors such as kidney, ovarian and prostate cancer, to see if siltuximab is safe and to determine what effects it has on these types of cancer. This study is being done in patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM) or Indolent Multiple Myeloma (IMM) to determine if siltuximab has an effect on heart function measured by ECG recordings, and more specifically to determine if siltuximab has any effect on the QT interval. MGUS, SMM and IMM patients usually go on to develop active multiple myeloma which is a type of cancer that affects the blood and bone marrow. The cancer cells in the bone marrow can cause the normal bone marrow cells to breakdown. This can result in low levels of red blood cells (which may make the patient feel tired or fatigued), low levels of white blood cells (which may increase the patient's chances of infections) or low levels of platelets (which may increase risk of bleeding). The cancer cells can cause damage to the normal bone. This can cause bone pain, bone fractures, and can increase the level of calcium in the blood. The cancer cells also make proteins (called M-proteins), which can result in damage to other organs, especially the kidneys. Siltuximab is a chimeric (part mouse and part human) antibody (immunoglobulin that is important for fighting infection). It does this by blocking another small protein called Interleukin 6 (IL-6). The body makes IL-6 naturally, and at normal levels it is important for the inflammatory response. But high levels of IL-6 can help cancer cells grow and interfere with chemotherapy drugs killing cancer cells. Cancer-related sicknesses such as weight loss, bone weakening, and depression have been linked to high levels of IL-6. This study will also look to see if siltuximab may be useful in treating patients with MGUS, SMM or IMM. All participating patients will be in the study for about 6 months and will receive siltuximab four (4) times every 3 weeks at a dose of 15mg per kg bodyweight. Siltuximab is given as a 1 hour intravenous infusion, through a small tube that goes directly into the vein. Following this treatment period, patients showing a response, defined as a 50% or higher reduction in M-protein in their blood/urine, may be allowed to continue treatment with siltuximab 15mg/kg every 4 weeks for up to 2 years.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • 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

  • Belgium
      • Antwerpen, Belgium
      • Gent, Belgium
  • Russian Federation
      • Izhevsk, Russian Federation
      • Moscow N/A, Russian Federation
      • Nizhni Novgorod, Russian Federation
  • United States
    • Illinois
      • Chicago, Illinois, United States
    • Texas
      • Dallas, Texas, United States
      • Houston, Texas, 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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of MGUS (measurable serum M-protein < 3 g/dL AND clonal bone marrow plasma cells < 10% without any end organ damage), SMM (measurable serum M-protein = 3 g/dL OR clonal bone marrow plasma cells = 10% without any end organ damage) or IMM (measurable serum M-protein = 3 g/dL OR clonal bone marrow plasma cells = 10% and = 3 lytic bone lesions but no other end organ damage)
  • Qualifying ECG results that will be checked by a central laboratory
  • Negative urine drug screen for substances of abuse
  • Qualifying hematology and chemistry laboratory results.

Exclusion Criteria:

  • Diagnosis of symptomatic multiple myeloma
  • Prior exposure to approved or investigational myeloma treatments
  • Prior exposure to agents targeting IL-6 or the IL-6 receptor
  • Significant cardiac disease
  • Skin condition likely to interfere with ECG electrode placement, breast implant, or thoracic surgery
  • Received medications known to affect the QT interval
  • Vaccination with live, attenuated vaccines within 4 weeks
  • Major surgery or radiation within 4 weeks

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 001
Siltuximab 15mg/kg IV infusion every 3 weeks for 4 cycles. If applicable extended dosing of 15 mg/kg IV infusion every 4 weeks for up to 2 years.
Biological: Siltuximab
15mg/kg IV infusion every 3 weeks for 4 cycles. If applicable extended dosing of 15 mg/kg IV infusion every 4 weeks for up to 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
QTc interval
Time Frame: Screening through Week 10
Screening through Week 10

Secondary Outcome Measures

Outcome Measure
Time Frame
Additional safety evaluations
Time Frame: 6 months and, if eligible, up to 2 years of extended treatment
6 months and, if eligible, up to 2 years of extended treatment
Efficacy evaluations
Time Frame: 6 months and, if eligible, up to 2 years of extended treatment
6 months and, if eligible, up to 2 years of extended treatment
Pharmacokinetic and Pharmacodynamic evaluations
Time Frame: 6 months and, if eligible, up to 2 years of extended treatment
6 months and, if eligible, up to 2 years of extended treatment

Collaborators and Investigators

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

Sponsor

Janssen Research & Development, LLC

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

October 1, 2010

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

September 23, 2010

First Submitted That Met QC Criteria

October 12, 2010

First Posted (Estimate)

October 13, 2010

Study Record Updates

Last Update Posted (Estimate)

January 19, 2015

Last Update Submitted That Met QC Criteria

January 16, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR017452
  • CNTO328SMM1001 (Other Identifier: Janssen Research & Development, LLC)

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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