A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma

Tracking Information
First Submitted Date ICMJE	December 1, 2011
First Posted Date ICMJE	December 2, 2011
Last Update Posted Date	February 5, 2018
Actual Study Start Date ICMJE	March 1, 2012
Estimated Primary Completion Date	August 31, 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 25, 2015)	One-year progression-free survival (PFS) rate [ Time Frame: 6 months after 74th participant is randomized ]; Defined by CRAB - IMWG (calcium, renal, anemia, and bone lesions - International Myeloma Working Group) criteria.
Original Primary Outcome Measures ICMJE; (submitted: December 1, 2011)	One-year progression-free survival (PFS) rate [ Time Frame: One year after randomization of last patient ]; Defined by CRAB - IMWG (calcium, renal, anemia, and bone lesions - International Myeloma Working Group) criteria.
Change History	Complete list of historical versions of study NCT01484275 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 25, 2015)	Progression-free survival (PFS) [ Time Frame: Up to approximately 4 years after randomization of last patient ]Based on CRAB criteria.; Progressive Disease (PD) indicator rate [ Time Frame: 6 months after 74th participant is randomized ]Novel composite endpoint, built from potential early signs of progression to multiple myeloma.; European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) [ Time Frame: Up to approximately 4 years after randomization of last patient ]The questionnaire includes 9 scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 6 single-item scales (dyspnea, insomnia, anorexia, constipation, diarrhea and financial impact) and single-item global health and quality of life scales.; Brief Pain Inventory (worst pain item) [ Time Frame: Up to approximately 4 years after randomization of last patient ]Refers to the "worst" pain the patient has experienced over the past 24 hours.; Changes in clinical laboratory values [ Time Frame: Up to approximately 4 years after randomization of last patient ]; Number of participants experiencing adverse events [ Time Frame: Up to approximately 4 years after randomization of last patient ]; Overall survival [ Time Frame: Approximately 4 years after randomization of last patient ]
Original Secondary Outcome Measures ICMJE; (submitted: December 1, 2011)	Progression-free survival (PFS) [ Time Frame: Up to approximately 4 years after randomization of last patient ]Based on CRAB criteria.; Progressive Disease (PD) indicator rate [ Time Frame: 6 months after randomization of last patient ]Novel composite endpoint, built from potential early signs of progression to multiple myeloma.; European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) [ Time Frame: Up to approximately 4 years after randomization of last patient ]The questionnaire includes 9 scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 6 single-item scales (dyspnea, insomnia, anorexia, constipation, diarrhea and financial impact) and single-item global health and quality of life scales.; Brief Pain Inventory (worst pain item) [ Time Frame: Up to approximately 4 years after randomization of last patient ]Refers to the "worst" pain the patient has experienced over the past 24 hours.; Changes in clinical laboratory values [ Time Frame: Up to approximately 4 years after randomization of last patient ]; Adverse events [ Time Frame: Up to approximately 4 years after randomization of last patient ]; Overall survival [ Time Frame: Approximately 4 years after randomization of last patient ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma
Official Title ICMJE	A Phase 2, Randomized, Blinded, Placebo-controlled, Multicenter Study of Siltuximab (Anti IL 6 Monoclonal Antibody) in Subjects With High-risk Smoldering Multiple Myeloma
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).
Detailed Description	This is a randomized (treatment assigned by chance), double-blind (neither patient nor investigator know which treatment is given), multicenter study to evaluate the safety and efficacy of siltuximab compared with placebo in patients with 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). Approximately 74 patients will receive either siltuximab or placebo by intravenous (IV, injection into a vein) infusion every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study (approximately 4 years after randomization of the last patient). Efficacy, pharmacokinetics, immunogenicity, and potential biomarkers will be assessed at time points defined in the protocol. Patient reported outcomes (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30, Brief Pain Inventory [worst pain], Non-Chemotherapy Anemia Symptom Scale) will be administered before any procedure or treatment at each visit. Patient safety will be monitored throughout the study.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	High-risk Smoldering Multiple Myeloma
Intervention ICMJE	Drug: Siltuximab 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.; Drug: Placebo 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.
Study Arms	Experimental: Siltuximab 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. Intervention: Drug: Siltuximab; Placebo Comparator: Placebo 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. Intervention: Drug: Placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: August 8, 2016)	87
Original Estimated Enrollment ICMJE; (submitted: December 1, 2011)	100
Estimated Study Completion Date	August 31, 2019
Estimated Primary Completion Date	August 31, 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 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 Exclusion Criteria: 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Belgium, France, Germany, Greece, Israel, Korea, Republic of, Spain, Sweden, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01484275
Other Study ID Numbers ICMJE	CR100755; CNTO328SMM2001 ( Other Identifier: Janssen Research & Development, LLC ); 2011-001735-22 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	Janssen Research & Development, LLC
Study Sponsor ICMJE	Janssen Research & Development, LLC
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account	Janssen Research & Development, LLC
Verification Date	February 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP