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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01484275
Registration number
NCT01484275
Ethics application status
Date submitted
1/12/2011
Date registered
2/12/2011
Date last updated
27/01/2020
Titles & IDs
Public title
A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma
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Scientific title
A Phase 2, Randomized, Blinded, Placebo-controlled, Multicenter Study of Siltuximab (Anti IL 6 Monoclonal Antibody) in Subjects With High-risk Smoldering Multiple Myeloma
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Secondary ID [1]
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CNTO328SMM2001
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Secondary ID [2]
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CR100755
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
High-risk Smoldering Multiple Myeloma
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Condition category
Condition code
Cancer
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Other cancer types
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Cancer
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Myeloma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Siltuximab
Treatment: Drugs - Placebo
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.
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.
Treatment: Drugs: 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.
Treatment: Drugs: 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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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One-Year Progression-Free Survival (PFS) Rate
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Assessment method [1]
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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).
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Timepoint [1]
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Up to 1 Year
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Secondary outcome [1]
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Progressive Disease Indicator Rate (PDIR) at 6 Months
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Assessment method [1]
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PDIR is defined as percentage of participants who meet any of following criteria occurring within 6 months of start of treatment. a) CRAB criteria: true progression events, b) Serum M-protein: increase by 25 % compared with baseline at 2 consecutive assessments, c) Magnetic resonance imaging: unequivocal increase in focal bone lesions, d) Immunoparesis: decrease by 25% compared with baseline of 2 other non-affected immunoglobulin (Ig) (IgG, IgM, IgA) at 2 consecutive assessments, e) Hemoglobin: decrease of 1.5 g/dL (with at least 1 read below LLN) at 2 consecutive assessments, with no other identifiable cause. PD is defined as presence of M-component in serum plus clonal plasma cells in bone marrow plus 1 or more of following: Calcium elevation (\> 11.5 mg/dL \[\> 2.88 mmol/L\]); Renal insufficiency (creatinine \>2 mg/dL \[177 micro mol/L or more\]); Anemia (hemoglobin \<10 or 2 g/dL lower than LLN) \[hemoglobin \< 6.5 or 1.25 mmol/L lower than LLN\]); Bone disease (lytic lesions or osteopenia).
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Timepoint [1]
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At 6 Months
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Secondary outcome [2]
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Progression-Free Survival
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Assessment method [2]
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PFS is defined as the time between randomization and initial documented PD according to the CRAB - International Myeloma Working Group (IMWG) criteria or date of death, whichever occurs first. 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 (\> 11.5 mg/dL \[\> 2.88 mmol/L\]); Renal insufficiency (creatinine \> 2 mg/dL \[177 \[micro mol/L or more\]); Anemia (\<10 g/dL or 2 g/dL) lower than LLN) \[hemoglobin \< 6.5 mmol/L or 1.25 mmol/L lower than LLN\]); Bone disease (lytic lesions or osteopenia).
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Timepoint [2]
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Up to 4.7 Years
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Secondary outcome [3]
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Percentage of Participants With Serum M-protein Response
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Assessment method [3]
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Serum M-protein response is defined as a decrease of greater than or equal to (\>=) 50% in serum M-protein compared with baseline at 2 consecutive assessments.
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Timepoint [3]
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Up to 4.7 Years
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Secondary outcome [4]
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Time to Worsening in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scale Score
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Assessment method [4]
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Time to worsening in EORTC-QLQ-C30 (physical function scale) is defined as time between randomization and first documentation of a worsening in EORTC-QLQ-C-30. Worsening in the EORTC-QLQ-C30 is defined as 10 points decrease from baseline. It comprises module with 30 items. Questionnaire includes 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, nausea/vomiting), a global health and quality of life scale, and a number of single items assessing symptoms (dyspnea, loss of appetite, insomnia, constipation, diarrhoea). Instrument contains 28 items using a Likert scale with 4 response options: "Not at All," "A Little," "Quite a Bit," "Very Much" (scored 1-4). Two additional items use response options (1-7): 1=Very Poor, to 7=Excellent. All scale and item scores were linearly transformed to be in range from 0-100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms.
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Timepoint [4]
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Up to 4.7 Years
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Secondary outcome [5]
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Time to Worsening in the Brief Pain Inventory (BPI) Worst Item Scores
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Assessment method [5]
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Time to worsening in the BPI worst item is defined as the time between randomization and the first documentation of a worsening in the BPI worst item. It has 2 domains reflecting pain severity and pain interference with domains of functioning and well-being. The selected item refers to the "worst" pain the patient has experienced over the past 24 hours. This item has been found to be most responsive to interference with key domains of functioning and well-being and may be used as a single item. Responses are provided on an 11-point numeric rating scale ranging from 0 "no pain" to 10 "pain as bad as you can imagine". Responses are described as mild (1 to 4), moderate (5 to 6) and severe (7 to 10). Worsening in the BPI worst item is defined as 2 points increase from baseline.
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Timepoint [5]
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Up to 4.7 Years
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Secondary outcome [6]
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Number of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features
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Assessment method [6]
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Number of participants who progressed to symptomatic multiple myeloma with stage III of International Staging System (ISS) or abnormal cytogenetic findings were assessed. The ISS system consists of stage I: beta2-microglobulin \< 3.5 milligram per liter (mg/L) and albumin \>= 3.5 gram (g)/100 ml; stage II: neither stage I nor stage III and stage III: beta2-microglobulin \>= 5.5 mg/L.
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Timepoint [6]
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Up to 4.7 Years
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Secondary outcome [7]
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Number of Participants With Best Response to First Subsequent Multiple Myeloma Treatment
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Assessment method [7]
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Best response to first subsequent anti-myeloma therapy was assessed by physician report at 6-month intervals and classified as: complete response (CR) (negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasms cells (PCs) in bone marrow); stringent CR (CR plus a normal FLC ratio, absence of clonal cells in bone marrow); near CR (\< 5% PCs in a bone marrow aspirate, no increase in lytic bone lesions); very good partial response (VGPR) (serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hour); partial response (PR): \>= 50 reduction of serum M-protein, reduction in 24-hour urinary M-protein by \>=90 % or to \< 200 mg/24 hours); minimal response (\>=25% but \<= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%); stable disease (not meeting criteria for CR, VGPR, PR, or PD); PD; not evaluable and unknown.
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Timepoint [7]
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Up to 4.7 Years
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Secondary outcome [8]
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Overall Survival (OS)
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Assessment method [8]
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OS is defined as the time between randomization and death due to any cause.
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Timepoint [8]
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Up to 4.7 Years
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Eligibility
Key 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
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Minimum age
18
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/03/2012
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
21/08/2019
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Sample size
Target
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Accrual to date
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Final
85
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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- Camperdown
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Recruitment hospital [2]
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- East Melbourne
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Recruitment hospital [3]
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- Randwick
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Recruitment postcode(s) [1]
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- Camperdown
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Recruitment postcode(s) [2]
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- East Melbourne
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Recruitment postcode(s) [3]
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- Randwick
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Recruitment outside Australia
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United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Michigan
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New York
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Pennsylvania
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South Carolina
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Texas
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Belgium
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Antwerpen
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Belgium
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Brussels
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Belgium
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Gent
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France
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Dijon
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France
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Nantes Cedex 1
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France
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Tours
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France
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Villejuif
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Germany
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Berlin
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Germany
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Hamburg
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Germany
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Heidelberg
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Greece
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Athens
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Israel
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Ashkelon
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Netanya
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Israel
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Petach Tikva
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Israel
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Tel Aviv
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Korea, Republic of
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Daejeon
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Seoul
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Spain
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Barcelona
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Spain
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Barcleona
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Spain
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Madrid
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Spain
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Salamanca
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Spain
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Valencia
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Sweden
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Göteborg
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Sweden
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Linkoping
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Sweden
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Stockholm
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United Kingdom
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London
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United Kingdom
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Janssen Research & Development, LLC
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Address
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Ethics approval
Ethics application status
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Summary
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).
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Trial website
https://clinicaltrials.gov/study/NCT01484275
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Trial related presentations / publications
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.
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Public notes
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Contacts
Principal investigator
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Janssen Research & Development, LLC Clinical Trial
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Address
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Janssen Research & Development, LLC
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01484275
Download to PDF