A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma
A Phase 2, Randomized, Blinded, Placebo-controlled, Multicenter Study of Siltuximab (Anti IL 6 Monoclonal Antibody) in Subjects With High-risk Smoldering Multiple Myeloma
3 other identifiers
interventional
85
11 countries
40
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of siltuximab compared with placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) in patients with high-risk smoldering multiple myeloma (SMM).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2012
Longer than P75 for phase_2
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 1, 2011
CompletedFirst Posted
Study publicly available on registry
December 2, 2011
CompletedStudy Start
First participant enrolled
March 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 12, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
August 21, 2019
CompletedResults Posted
Study results publicly available
January 27, 2020
CompletedJanuary 27, 2020
January 1, 2020
3.2 years
December 1, 2011
December 20, 2019
January 23, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
One-Year Progression-Free Survival (PFS) Rate
One-year PFS rate is defined as the percentage (%) of participants surviving 1 year after randomization without progression to multiple myeloma or death estimated by the Kaplan-Meier method and based on the International Myeloma Working Group (IMWG) calcium, renal, anemia, and bone lesions (CRAB) criteria. Progressive disease (PD) is defined as presence of an M- component in serum plus clonal plasma cells in the bone marrow plus 1 or more of the following: Calcium elevation (greater than \[\>\] 11.5 milligram per deciliter \[mg/dL\] \[\> 2.88 millimoles per liter {mmol/L}\]); Renal insufficiency (creatinine \> 2 mg/dL \[177 micromoles per liter or more\]; Anemia (hemoglobin less than \[\<\] 10 gram per deciliter \[g/dL\] or 2 g/dL lower than lower limit of normal \[LLN\] \[hemoglobin \< 6.5 mmol/L or 1.25 mmol/L lower than LLN\]); Bone disease (lytic lesions or osteopenia).
Up to 1 Year
Secondary Outcomes (8)
Progressive Disease Indicator Rate (PDIR) at 6 Months
At 6 Months
Progression-Free Survival
Up to 4.7 Years
Percentage of Participants With Serum M-protein Response
Up to 4.7 Years
Time to Worsening in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scale Score
Up to 4.7 Years
Time to Worsening in the Brief Pain Inventory (BPI) Worst Item Scores
Up to 4.7 Years
- +3 more secondary outcomes
Study Arms (2)
Siltuximab
EXPERIMENTALType=exact, unit=mg/kg, number=15, form=intravenous infusion, route=intravenous use, every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study.
Placebo
PLACEBO COMPARATORForm=intravenous infusion, route=intravenous use route=intravenous, use every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study.
Interventions
Type=exact, unit=mg/kg, number=15, form=intravenous infusion, route=intravenous use, every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study.
Form=intravenous infusion, route=intravenous use route=intravenous, use every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study.
Eligibility Criteria
You may qualify if:
- Diagnosis of smoldering multiple myeloma (SMM) for \<4 years
- Diagnosis of high-risk SMM (defined as bone marrow plasma cells \>=10% and either serum monoclonal protein \>=3 g/dL, or abnormal free light chain ratio \<0.126 or \>8 and serum M-protein \<3 g/dL but \>=1 g/dL)
- Patients must be within certain limits for protocol-specified laboratory tests
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Women not of childbearing potential must be postmenopausal, permanently sterilized, or otherwise incapable of pregnancy
- Women of childbearing potential must agree to use adequate birth control measures and agree to not donate eggs for the purpose of assisted reproduction during the study and for 3 months after receiving the last dose of study agent, and must have a negative pregnancy test at screening
- Men must agree to use a double-barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study agent
You may not qualify if:
- Having symptomatic multiple myeloma, defined by any of the following (if due to myeloma): lytic bone lesions, severe osteopenia (low bone density), pathologic fractures, hypercalcemia (too much calcium in the blood), kidney insufficiency; symptomatic hyperviscosity of the blood, or recurrent serious bacterial infections such as pneumonia
- Primary systemic amyloid light (AL) chain amyloidosis (a build-up of amyloid light chain proteins in the blood)
- Prior or concurrent exposure to approved or investigational multiple myeloma treatments (concurrent treatment with bone-protecting agents (eg, bisphosphonates, denosumab), or steroids (not exceeding 10 mg prednisone per day or equivalent) are only allowed if given in a stable dose and for a nonmalignant condition; concurrent treatment with erythropoietin-stimulating agents (ESAs) are not allowed.)
- Prior exposure to agents targeting interleukin 6 (IL 6) or the IL 6 receptor
- Other malignancy within the past 3 years, except for the following, if treated and not active: basal cell or nonmetastatic (non-spreading) squamous cell carcinoma of the skin, cervical carcinoma or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (40)
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Rockville, Maryland, United States
Unknown Facility
Detroit, Michigan, United States
Unknown Facility
New York, New York, United States
Unknown Facility
Kittanning, Pennsylvania, United States
Unknown Facility
Philadelphia, Pennsylvania, United States
Unknown Facility
Greenville, South Carolina, United States
Unknown Facility
Dallas, Texas, United States
Unknown Facility
Camperdown, Australia
Unknown Facility
East Melbourne, Australia
Unknown Facility
Randwick, Australia
Unknown Facility
Antwerp, Belgium
Unknown Facility
Brussels, Belgium
Unknown Facility
Ghent, Belgium
Unknown Facility
Dijon, France
Unknown Facility
Nantes, France
Unknown Facility
Tours, France
Unknown Facility
Villejuif, France
Unknown Facility
Berlin, Germany
Unknown Facility
Hamburg, Germany
Unknown Facility
Heidelberg, Germany
Unknown Facility
Athens, Greece
Unknown Facility
Ashkelon, Israel
Unknown Facility
Jerusalem, Israel
Unknown Facility
Nahariya, Israel
Unknown Facility
Netanya, Israel
Unknown Facility
Petah Tikva, Israel
Unknown Facility
Tel Aviv, Israel
Unknown Facility
Daejeon, South Korea
Unknown Facility
Seoul, South Korea
Unknown Facility
Barcelona, Spain
Unknown Facility
Barcleona, Spain
Unknown Facility
Madrid, Spain
Unknown Facility
Salamanca, Spain
Unknown Facility
Valencia, Spain
Unknown Facility
Gothenburg, Sweden
Unknown Facility
Linköping, Sweden
Unknown Facility
Stockholm, Sweden
Unknown Facility
London, United Kingdom
Unknown Facility
Manchester, United Kingdom
Related Publications (1)
Brighton TA, Khot A, Harrison SJ, Ghez D, Weiss BM, Kirsch A, Magen H, Gironella M, Oriol A, Streetly M, Kranenburg B, Qin X, Bandekar R, Hu P, Guilfoyle M, Qi M, Nemat S, Goldschmidt H. Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Siltuximab in High-Risk Smoldering Multiple Myeloma. Clin Cancer Res. 2019 Jul 1;25(13):3772-3775. doi: 10.1158/1078-0432.CCR-18-3470. Epub 2019 Mar 19.
PMID: 30890552DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Siltuximab demonstrated positive trending toward 1-year PFS only in high risk SMM-group. Sponsor and Steering Committee decided not to further pursue clinical development of siltuximab for SMM and terminated study, and was considered as completed.
Results Point of Contact
- Title
- Senior Director
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 1, 2011
First Posted
December 2, 2011
Study Start
March 1, 2012
Primary Completion
May 12, 2015
Study Completion
August 21, 2019
Last Updated
January 27, 2020
Results First Posted
January 27, 2020
Record last verified: 2020-01