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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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
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
Secondary ID [1] 0 0
CNTO328SMM2001
Secondary ID [2] 0 0
CR100755
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High-risk Smoldering Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Myeloma

Intervention/exposure
Study type
Interventional
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
Up to 1 Year
Secondary outcome [1] 0 0
Progressive Disease Indicator Rate (PDIR) at 6 Months - 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).
Timepoint [1] 0 0
At 6 Months
Secondary outcome [2] 0 0
Progression-Free Survival - 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).
Timepoint [2] 0 0
Up to 4.7 Years
Secondary outcome [3] 0 0
Percentage of Participants With Serum M-protein Response - 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.
Timepoint [3] 0 0
Up to 4.7 Years
Secondary outcome [4] 0 0
Time to Worsening in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scale Score - 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.
Timepoint [4] 0 0
Up to 4.7 Years
Secondary outcome [5] 0 0
Time to Worsening in the Brief Pain Inventory (BPI) Worst Item Scores - 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.
Timepoint [5] 0 0
Up to 4.7 Years
Secondary outcome [6] 0 0
Number of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features - 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.
Timepoint [6] 0 0
Up to 4.7 Years
Secondary outcome [7] 0 0
Number of Participants With Best Response to First Subsequent Multiple Myeloma Treatment - 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.
Timepoint [7] 0 0
Up to 4.7 Years
Secondary outcome [8] 0 0
Overall Survival (OS) - OS is defined as the time between randomization and death due to any cause.
Timepoint [8] 0 0
Up to 4.7 Years

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- East Melbourne
Recruitment hospital [3] 0 0
- Randwick
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- East Melbourne
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Belgium
State/province [8] 0 0
Antwerpen
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussels
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
France
State/province [11] 0 0
Dijon
Country [12] 0 0
France
State/province [12] 0 0
Nantes Cedex 1
Country [13] 0 0
France
State/province [13] 0 0
Tours
Country [14] 0 0
France
State/province [14] 0 0
Villejuif
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Germany
State/province [17] 0 0
Heidelberg
Country [18] 0 0
Greece
State/province [18] 0 0
Athens
Country [19] 0 0
Israel
State/province [19] 0 0
Ashkelon
Country [20] 0 0
Israel
State/province [20] 0 0
Jerusalem
Country [21] 0 0
Israel
State/province [21] 0 0
Nahariya
Country [22] 0 0
Israel
State/province [22] 0 0
Netanya
Country [23] 0 0
Israel
State/province [23] 0 0
Petach Tikva
Country [24] 0 0
Israel
State/province [24] 0 0
Tel Aviv
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Daejeon
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Barcleona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Spain
State/province [30] 0 0
Salamanca
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia
Country [32] 0 0
Sweden
State/province [32] 0 0
Göteborg
Country [33] 0 0
Sweden
State/province [33] 0 0
Linkoping
Country [34] 0 0
Sweden
State/province [34] 0 0
Stockholm
Country [35] 0 0
United Kingdom
State/province [35] 0 0
London
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

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).
Trial website
https://clinicaltrials.gov/show/NCT01484275
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications