Back to resultsAn Efficacy and Safety Study of Siltuximab in Participants With Relapsed or Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Siltuximab
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Myeloma, Intravenous, Monoclonal antibody, Siltuximab, Dexamethasone, CNTO 328
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of multiple myeloma with relapsed or refractory disease after failing at least 2 prior lines of therapy
- Prior treatment regimen must have included bortezomib (alone or in combination with other agents)
- Measurable secretory disease defined as either serum monoclonal paraprotein (M- protein) greater than or equal to (>=) 1 gram per deciliter (g/dL) or urine monoclonal (light chain) protein (greater than (>) 200 milligram/24 hours)
- Eastern Cooperative Oncology Group (ECOG) performance status score of less than or equal to (<=) 2 - Participants of childbearing potential must use adequate birth control measures, female participants of childbearing potential must have a negative serum pregnancy test at screening
Exclusion Criteria:
- Treatment with systemic cancer therapy (including clarithromycin) or radiotherapy within 30 days before the first dose of study agent - Treatment with nitrosoureas (a group of alkylating agents used as antineoplastic drugs in the chemotherapy) within 42 days before the first dose of study agent
- Major surgery within 30 days before the first dose of study agent or planning to have surgery (except for minor surgical procedures) during the study
- Serious concurrent illness (medical or psychiatric), uncontrolled infection, or significant cardiac disease characterized by significant ischemic coronary disease (an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow) or congestive heart failure (condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body) not under medical control, or any uncontrolled medical condition (for example: uncontrolled diabetes), including the presence of clinical laboratory abnormalities, that places the subject at unacceptable risk by participating in the study or confounds the ability to interpret data from the study
- Known to be seropositive (giving a positive result in a test of blood serum) for Human Immunodeficiency Virus (HIV), or active hepatitis A, B or C infection
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Treatment Plan A
Treatment Plan B
Arm Description
Siltuximab 6 milligram per kilogram (mg/kg) as intravenous (directly into the vein) infusion once every 2 weeks for 12 cycles and duration of each cycle is 28 days (if participant have complete or partial response) along with dexamethasone (starting from Cycle 2, If participant do not have complete or partial response) 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles after that on Day 1 to 4 up to 12 cycles.
Siltuximab 6 mg/kg as intravenous infusion once every 2 weeks along with dexamethasone 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles (duration of each cycle is 28 days) after that on Day 1 to 4 up to 12 cycles.
Outcomes
Primary Outcome Measures
Percentage of Participants With Overall Response
The overall response is defined as percentage of participants having confirmed Complete Response (CR) and Partial Response (PR) by using the European Group for Blood and Marrow Transplantation (EBMT) criteria. CR is absence of the original monoclonal protein (M-protein) in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas. PR is greater than or equal to (>=) 50 percent reduction in the level of the serum M-protein maintained for a minimum of 6 weeks and >= 50 percent reduction in the size of soft tissue plasmacytomas.
Secondary Outcome Measures
Time to Progression (TTP)
The TTP is defined as the time interval in days between the date of first administration of study treatment (as monotherapy or as combination therapy) to the date of first documented evidence of confirmed progressive disease (including relapse from CR). CR is absence of the original M-protein in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas.
Duration of Response
The duration of response is defined as the time from initial documented response (Complete Response [CR] or Partial Response [PR]), to the first documented sign of progression. CR is absence of the original M-protein in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas. PR is >= 50% reduction in the level of the serum M-protein maintained for a minimum of 6 weeks and >= 50% reduction in the size of soft tissue plasmacytomas.
Number of Participants With Immune Response
Immune response is defined as antibody (type of protein that helps to protect the body against foreign matter, such as bacteria and viruses) response to siltuximab.
Percent Change From Baseline in C-Reactive Protein (CRP) Level
Percentage change in CRP is equal to CRP at time of measurement minus CRP at baseline divided by CRP at baseline multiplied by 100.
Percent Change From Baseline in C-telopeptide (CTx) Level
Percentage change in CTx is equal to CTx at time of measurement minus CTx at baseline divided by CTx at baseline multiplied by 100.
Percent Change From Baseline in N-telopeptide (NTx) Level
Percentage change in NTx is equal to NTx at time of measurement minus NTx at baseline divided by NTx at baseline multiplied by 100.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00402181
Brief Title
An Efficacy and Safety Study of Siltuximab in Participants With Relapsed or Refractory Multiple Myeloma
Official Title
A Phase 2 Multicenter Study of CNTO 328 (Anti IL-6 Monoclonal Antibody) in Subjects With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of siltuximab in participants with relapsed (the return of a disease or the signs and symptoms of a disease after a period of improvement.) or refractory (cancer that does not respond to treatment) multiple myeloma (a type of cancer that begins in plasma cells [white blood cells that produce antibodies]).
Detailed Description
This is an open-label (all people know the identity of the intervention), multicenter (when more than one hospital or medical school team work on a medical research study), non-randomized (a clinical trial in which the participants are not assigned by chance to different treatment groups), prospective (study following participants forward in time) safety and efficacy study of siltuximab in participants with relapsed or refractory multiple myeloma. The study consists of 3 Phases: Screening Phase (from first visit until the first dose of study drug), Treatment Phase (from the first dose to the end-of-treatment), and Follow-up Phase (after end-of-treatment until the end of study). The duration of participation in the study for an individual participant will be up to 4 weeks for Screening Phase, approximately 52 weeks for Treatment Phase and until death, lost to follow-up, withdraw of consent or end of study, whichever, comes first for Follow-up Phase. Treatment will be administered on a 28-day cycle. The study is designed with 2 alternative treatment plans. Treatment Plan A: during first 2 cycles siltuximab will be administered alone, dexamethasone may be added to the treatment regimen based on the participant's response to treatment. Treatment Plan B: siltuximab and dexamethasone combination for the duration of the study. The first 14 eligible participants will follow Treatment Plan A and data evaluation will be conducted for participants after 2 cycles of treatment and 2 post baseline disease assessments. If at least one complete response (CR) or partial response (PR) is observed in 14 participants, all subsequent participants will follow Treatment Plan A. However, if no responses (CR or PR) are observed, all subsequent participants will follow Treatment Plan B. The primary efficacy endpoint will be percentage of participants with overall response. Participants' safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Myeloma, Intravenous, Monoclonal antibody, Siltuximab, Dexamethasone, CNTO 328
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Plan A
Arm Type
Experimental
Arm Description
Siltuximab 6 milligram per kilogram (mg/kg) as intravenous (directly into the vein) infusion once every 2 weeks for 12 cycles and duration of each cycle is 28 days (if participant have complete or partial response) along with dexamethasone (starting from Cycle 2, If participant do not have complete or partial response) 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles after that on Day 1 to 4 up to 12 cycles.
Arm Title
Treatment Plan B
Arm Type
Experimental
Arm Description
Siltuximab 6 mg/kg as intravenous infusion once every 2 weeks along with dexamethasone 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles (duration of each cycle is 28 days) after that on Day 1 to 4 up to 12 cycles.
Intervention Type
Biological
Intervention Name(s)
Siltuximab
Other Intervention Name(s)
CNTO 328
Intervention Description
Siltuximab 6 mg/kg as intravenous infusion once every 2 weeks for 12 cycles and duration of each cycle is 28 days.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 40 mg tablet orally on Day 1 to 4, 9 to 12 and 17 to 20 for maximum 4 cycles after that on Day 1 to 4 up to 12 cycles and duration of each cycle is 28 days.
Primary Outcome Measure Information:
Title
Percentage of Participants With Overall Response
Description
The overall response is defined as percentage of participants having confirmed Complete Response (CR) and Partial Response (PR) by using the European Group for Blood and Marrow Transplantation (EBMT) criteria. CR is absence of the original monoclonal protein (M-protein) in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas. PR is greater than or equal to (>=) 50 percent reduction in the level of the serum M-protein maintained for a minimum of 6 weeks and >= 50 percent reduction in the size of soft tissue plasmacytomas.
Time Frame
Baseline up to end of study (Day 807)
Secondary Outcome Measure Information:
Title
Time to Progression (TTP)
Description
The TTP is defined as the time interval in days between the date of first administration of study treatment (as monotherapy or as combination therapy) to the date of first documented evidence of confirmed progressive disease (including relapse from CR). CR is absence of the original M-protein in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas.
Time Frame
Baseline up to end of study (Day 807)
Title
Duration of Response
Description
The duration of response is defined as the time from initial documented response (Complete Response [CR] or Partial Response [PR]), to the first documented sign of progression. CR is absence of the original M-protein in serum and urine maintained for a minimum of 6 weeks, and disappearance of soft tissue plasmacytomas. PR is >= 50% reduction in the level of the serum M-protein maintained for a minimum of 6 weeks and >= 50% reduction in the size of soft tissue plasmacytomas.
Time Frame
Baseline up to end of study (Day 807)
Title
Number of Participants With Immune Response
Description
Immune response is defined as antibody (type of protein that helps to protect the body against foreign matter, such as bacteria and viruses) response to siltuximab.
Time Frame
Day 1 (Cycle 1 [pre-dose]), treatment discontinuation, and every 3 months after the last dose (up to 3 times)
Title
Percent Change From Baseline in C-Reactive Protein (CRP) Level
Description
Percentage change in CRP is equal to CRP at time of measurement minus CRP at baseline divided by CRP at baseline multiplied by 100.
Time Frame
Before siltuximab administration in Cycles 1, 2, and 3 on Days 1 and 15; thereafter, on Day 1 of each cycle up to12 cycles
Title
Percent Change From Baseline in C-telopeptide (CTx) Level
Description
Percentage change in CTx is equal to CTx at time of measurement minus CTx at baseline divided by CTx at baseline multiplied by 100.
Time Frame
Before siltuximab administration on Day 1 of cycles 1, 2, and 3
Title
Percent Change From Baseline in N-telopeptide (NTx) Level
Description
Percentage change in NTx is equal to NTx at time of measurement minus NTx at baseline divided by NTx at baseline multiplied by 100.
Time Frame
Before siltuximab administration on Day 1 of cycles 1, 2, and 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of multiple myeloma with relapsed or refractory disease after failing at least 2 prior lines of therapy
Prior treatment regimen must have included bortezomib (alone or in combination with other agents)
Measurable secretory disease defined as either serum monoclonal paraprotein (M- protein) greater than or equal to (>=) 1 gram per deciliter (g/dL) or urine monoclonal (light chain) protein (greater than (>) 200 milligram/24 hours)
Eastern Cooperative Oncology Group (ECOG) performance status score of less than or equal to (<=) 2 - Participants of childbearing potential must use adequate birth control measures, female participants of childbearing potential must have a negative serum pregnancy test at screening
Exclusion Criteria:
Treatment with systemic cancer therapy (including clarithromycin) or radiotherapy within 30 days before the first dose of study agent - Treatment with nitrosoureas (a group of alkylating agents used as antineoplastic drugs in the chemotherapy) within 42 days before the first dose of study agent
Major surgery within 30 days before the first dose of study agent or planning to have surgery (except for minor surgical procedures) during the study
Serious concurrent illness (medical or psychiatric), uncontrolled infection, or significant cardiac disease characterized by significant ischemic coronary disease (an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow) or congestive heart failure (condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body) not under medical control, or any uncontrolled medical condition (for example: uncontrolled diabetes), including the presence of clinical laboratory abnormalities, that places the subject at unacceptable risk by participating in the study or confounds the ability to interpret data from the study
Known to be seropositive (giving a positive result in a test of blood serum) for Human Immunodeficiency Virus (HIV), or active hepatitis A, B or C infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor, Inc. Clinical Trial
Organizational Affiliation
Centocor, Inc.
Official's Role
Study Director
Facility Information:
City
Duarte
State/Province
California
Country
United States
City
Norwalk
State/Province
Connecticut
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
New York
State/Province
New York
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
N Charleston
State/Province
South Carolina
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Amsterdam
Country
Netherlands
City
Den Haag
Country
Netherlands
City
Leiden
Country
Netherlands
City
Rotterdam
Country
Netherlands
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=175&filename=CR012631_CSR.pdf
Description
A Phase 2 Multicenter Study of CNTO 328 (Anti IL-6 Monoclonal Antibody) in Subjects With Relapsed or Refractory Multiple Myeloma
Learn more about this trial
An Efficacy and Safety Study of Siltuximab in Participants With Relapsed or Refractory Multiple Myeloma
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