A Study to Compare CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone (VMP) With VMP Alone in Previously Untreated Multiple Myeloma Patients

November 17, 2014 updated by: Janssen Research & Development, LLC

A Randomized, Open-Label, Phase 2 Study of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and VELCADE-Melphalan-Prednisone Compared With VELCADE-Melphalan-Prednisone for the Treatment of Previously Untreated Multiple Myeloma

The purpose of this study is to evaluate safety and effectiveness of CNTO 328 (siltuximab) when it is administered together with velcade-melphalan-prednisone (VMP) in comparison with VMP alone in participants with multiple myeloma (a type of cancer that affects the blood and bone marrow).

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

The study will be conducted in 2 parts (Part 1 and Part 2) and will consist of screening period up to 2 weeks; treatment period; maintenance period (CNTO 328 hereafter referred to as siltuximab) for a maximum of 18 months and follow up period until the study ends. Part 1 is an open-label (all people know the identity of the intervention), single group safety lead-in part to evaluate the safety of siltuximab. Approximately 12 patients will be treated with siltuximab in combination with VMP. If the safety profile of the combination is acceptable, the study will proceed to Part 2. Part 2 is a randomized (the study medication is assigned by chance), open-label, 2-arm (Arm A: siltuximab + VMP; Arm B: VMP alone) study. Approximately 104 patients will be equally randomized, followed by a maintenance period with siltuximab in particiants in Arm A who achieve a partial response (PR) or better. Particiants in both parts of the study will be treated up to a maximum of nine 6-week cycles provided there is no evidence of disease progression, unacceptable toxicity, or withdrawal from treatment. Study medication will be continued for at least 2 additional cycles after confirmation of complete response, and preferably for the full 9 cycles of the treatment period. Participants who will be receiving maintenance treatment after the 12-month effectiveness analysis may continue to receive treatment with siltuximab only after careful consideration by the treating physician and on evidence of clinical benefit and in the absence of unwarranted toxicities. Safety assessments will include evaluation of adverse events, clinical laboratory tests, eastern cooperative oncology group performance status, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study.

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.
118

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 2

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

  • Australia
      • Adelaide, Australia
      • Melbourne, Australia
  • France
      • Bordeaux Cedex, France
      • Montpellier, France
      • Strasbourg, France
  • India
      • Ahmedabad, India
      • Calicut, India
      • Hyderabad N/A, India
      • Jaipur, India
      • Mumbai, India
  • Israel
      • Afula, Israel
      • Haifa, Israel
      • Jerusalem, Israel
      • Petah Tikva, Israel
      • Ramat-Gan, Israel
  • Korea, Republic of
      • Seoul, Korea, Republic of
  • Poland
      • Bialystok, Poland
      • Chorzów, Poland
      • Gdynia, Poland
      • Lodz, Poland
      • Wroclaw, Poland
  • Romania
      • Baia Mare, Romania
      • Brasov, Romania
      • Iasi, Romania
  • Russian Federation
      • Arkhangelsk, Russian Federation
      • Moscow N/A, Russian Federation
      • Nizhni Novgorod, Russian Federation
      • St. Petersburg, Russian Federation
  • Singapore
      • Singapore, Singapore
  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Murcia N/A, Spain
      • Salamanca, Spain
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Texas
      • 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

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:

  • Confirmed diagnosis of previously untreated multiple myeloma and not a candidate for high dose chemotherapy with stem cell transplantation
  • Eastern cooperative oncology group performance status score of less than or equal to 2
  • Measurable secretory disease, defined as either serum monoclonal paraprotein greater than or equal to 1 g/dL or urine monoclonal protein greater than 200 mg/24 hours
  • Adequate laboratory results that will be confirmed by a study physician
  • Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

  • Diagnosed with primary amyloidosis, asymptomatic or smoldering multiple myeloma or monoclonal gammopathy of undetermined significance
  • Diagnosed with Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
  • Received prior or current systemic therapy or stem cell transplantation for multiple myeloma
  • Peripheral neuropathy or neuropathic pain (Grade 2 or higher)
  • Received radiation therapy, plasmapheresis or surgery within 14 days
  • Transplanted solid organ, with the exception of a corneal transplant
  • Serious concurrent illness or history of uncontrolled heart disease

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: Randomized
  • Interventional Model: Parallel 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: Part 1: VMP+Siltuximab 11 mg/kg
Siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP (Velcade+Melphalan+Prednisone). Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally (by mouth).
Drug: Siltuximab11 mg/kg
Participants will receive siltuximab 11 mg/kg as a 1-hour intravenous infusion every 3 weeks in Part 1.
Other Names:
  • CNTO 328
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert in Part 1.
Other Names:
  • bortezomib
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)
Other Names:
  • bortezomib
Drug: Melphalan
Participants will take melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Drug: Melphalan
Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.
Other Names:
  • bortezomib
Drug: Melphalan
Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 orally according to the package insert.
Experimental: Part 2, Arm A: VMP+Siltuximab 8.3 mg/kg or 11 mg/kg
Siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks along with VMP. Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert in Part 1.
Other Names:
  • bortezomib
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)
Other Names:
  • bortezomib
Drug: Melphalan
Participants will take melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Drug: Melphalan
Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.
Other Names:
  • bortezomib
Drug: Melphalan
Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 orally according to the package insert.
Drug: Siltuximab 8.3 mg/kg or 11 mg/kg
Participants will receive siltuximab 8.3 mg/kg or 11 mg/kg as a 1-hour intravenous infusion every 3 weeks for 9 cycles of treatment in Part 2, Arm A and in maintenance period.
Other Names:
  • CNTO 328
Active Comparator: Part 2, Arm B: VMP
Velcade 1.3 mg/m2 will be administered as an intravenous bolus injection according to the current approved package inserts. Melphalan 9 mg/m2 and prednisone 60 mg/m2 will be taken orally
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert in Part 1.
Other Names:
  • bortezomib
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection for 9 cycles of the treatment period in Part 2. It will be administered twice weekly for first 4 cycles (on Days 1, 4, 8, 11, 22, 25, 29, and 32, followed by a 10-day rest period) and once weekly for next 5 cycles (on Days 1, 8, 22, and 29, followed by a 13-day rest period)
Other Names:
  • bortezomib
Drug: Melphalan
Participants will take melphalan 9 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Drug: Melphalan
Participants will receive melphalan according to currently approved package inserts. Melphalan 9 mg/m2 will be administered orally for 9 cycles of treatment period in Part 2, Arm A.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 will be administered orally on Days 1 to 4, followed by a 38-day rest period in Part 1.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 orally for 9 cycles of treatment period in Part 2, Arm A.
Drug: Velcade (bortezomib)
Participants will receive Velcade 1.3 mg/m2 as an intravenous bolus injection according to the current approved package insert.
Other Names:
  • bortezomib
Drug: Melphalan
Participants will take melphalan 9 mg/m2 orally according to currently approved package insert.
Drug: Prednisone
Participants will take prednisone 60 mg/m2 orally according to the package insert.

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
Percentage of Participants Who Achieved Complete Response (CR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
Time Frame: Up to disease progression, approximately 3 years
CR was assessed using EMBT criteria: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, <5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks.
Up to disease progression, approximately 3 years

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
Percentage of Participants Who Achieved Overall Response ie, Complete Response (CR) or Partial Response (PR) - European Group for Blood and Marrow Transplantation (EBMT) Criteria
Time Frame: Up to disease progression, approximately 3 years
CR or PR was assessed using EBMT criteria. CR: disappearance of the original monoclonal paraprotein from the blood and urine on at least 2 determinations for a minimum of 6 weeks by immunofixation studies, <5% plasma cells in the bone marrow on at least 1 determination, if skeletal survey is available: no increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response), disappearance of soft tissue plasmacytomas for at least 6 weeks; PR: >=50% reduction in the level of serum monoclonal paraprotein for at least 2 determinations 6 weeks apart, if present, reduction in 24-hour urinary light chain excretion by either >=90% or to <200 mg for at least 2 determinations 6 weeks apart, >=50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least 6 weeks, if skeletal survey is available: no increase in size or number of lytic bone lesions
Up to disease progression, approximately 3 years
Percentage of Participants Who Achieved Stringent Complete Response (sCR) - International Myeloma Working Group (IMWG) Criteria
Time Frame: Up to disease progression, approximately 3 years
sCR was assesses by IMWG Criteria: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, <=5% plasma cells in bone marrow, normal free light chain ratio, absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. sCR is a CR that has been confirmed by immunofixation + free light chain assay + either bone marrow immunohistochemistry or immunofluorescence
Up to disease progression, approximately 3 years
Progression-Free Survival (PFS)
Time Frame: From the date of randomization until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 3 years)
PFS was defined as the time between randomization and either disease progression or death, whichever occurred first.
From the date of randomization until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 3 years)
1-year Progression-Free Survival (PFS) Rate
Time Frame: 1 year
The 1-year PFS rate was defined as the percentage of participants surviving 1 year after randomization without disease progression or death.
1 year
Duration of Response (DOR)
Time Frame: From the date participants achieved CR or PR to either date for disease progression (including relapse from CR) or the censoring date for progressive disease, as assessed Up to 30 days after last dose of study medication
DOR was defined as length from the earliest date a participant achieved a complete response (CR) or partial response (PR) to either date for disease progression (including relapse from CR) or the censoring date for progressive disease. Responders without disease progression were censored at the last efficacy assessment for disease progression.
From the date participants achieved CR or PR to either date for disease progression (including relapse from CR) or the censoring date for progressive disease, as assessed Up to 30 days after last dose of study medication
1-year Survival Rate
Time Frame: 1 year
Percentage of participants who are alive at the end of year 1 after randomization
1 year
Overall Survival
Time Frame: From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)
Overall survival is defined as the time interval in days between the date of randomization and the participant's death from any cause.
From the date of randomization till the date of death, as assessed up to the end of study (approximately 3 years)
Change From Baseline to Cycle 9 in Global Health Status/Quality of Life Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30)
Time Frame: Baseline (Day 1 predose) and Cycle 9 (Week 54)
Global health status/quality of life is a subscale of the EORTC QOL C30, which comprises two questions related to overall health/quality of life during the past week. The raw score to each question ranged from 1 (very poor) to 7 (excellent). The raw mean score of health status/quality of life subscale is calculated for each participant and a linear transformation applied to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") health and quality of life.
Baseline (Day 1 predose) and Cycle 9 (Week 54)

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.
Janssen Research & Development, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Research & Development L.L.C Clinical Trial, Janssen Research & Development L.L.C

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.

General Publications

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.
June 1, 2009

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, 2013

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, 2013

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).
May 29, 2009

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.
May 29, 2009

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.
June 2, 2009

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.
November 18, 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.
November 17, 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.
November 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.
  • CR015901
  • CNTO328MMY2001 (Other Identifier: Janssen Research & Development, LLC)
  • 2008-007157-12 (EudraCT Number)

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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