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Trial record 2 of 2 for:    smm2001

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01484275
Recruitment Status : Completed
First Posted : December 2, 2011
Results First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

Condition or disease Intervention/treatment Phase
High-risk Smoldering Multiple Myeloma Drug: Siltuximab Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 1, 2012
Actual Primary Completion Date : May 12, 2015
Actual Study Completion Date : August 21, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Siltuximab

Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. One-Year Progression-Free Survival (PFS) Rate [ Time Frame: Up to 1 Year ]
    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).


Secondary Outcome Measures :
  1. Progressive Disease Indicator Rate (PDIR) at 6 Months [ Time Frame: 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).

  2. Progression-Free Survival [ Time Frame: Up to 4.7 Years ]
    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).

  3. Percentage of Participants With Serum M-protein Response [ Time Frame: Up to 4.7 Years ]
    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.

  4. Time to Worsening in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scale Score [ Time Frame: Up to 4.7 Years ]
    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.

  5. Time to Worsening in the Brief Pain Inventory (BPI) Worst Item Scores [ Time Frame: Up to 4.7 Years ]
    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.

  6. Number of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features [ Time Frame: Up to 4.7 Years ]
    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.

  7. Number of Participants With Best Response to First Subsequent Multiple Myeloma Treatment [ Time Frame: Up to 4.7 Years ]
    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.

  8. Overall Survival (OS) [ Time Frame: Up to 4.7 Years ]
    OS is defined as the time between randomization and death due to any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01484275


Locations
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United States, Illinois
Chicago, Illinois, United States
United States, Maryland
Rockville, Maryland, United States
United States, Michigan
Detroit, Michigan, United States
United States, New York
New York, New York, United States
United States, Pennsylvania
Kittanning, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
United States, South Carolina
Greenville, South Carolina, United States
United States, Texas
Dallas, Texas, United States
Australia
Camperdown, Australia
East Melbourne, Australia
Randwick, Australia
Belgium
Antwerpen, Belgium
Brussels, Belgium
Gent, Belgium
France
Dijon, France
Nantes Cedex 1, France
Tours, France
Villejuif, France
Germany
Berlin, Germany
Hamburg, Germany
Heidelberg, Germany
Greece
Athens, Greece
Israel
Ashkelon, Israel
Jerusalem, Israel
Nahariya, Israel
Netanya, Israel
Petach Tikva, Israel
Tel Aviv, Israel
Korea, Republic of
Daejeon, Korea, Republic of
Seoul, Korea, Republic of
Spain
Barcelona, Spain
Barcleona, Spain
Madrid, Spain
Salamanca, Spain
Valencia, Spain
Sweden
Göteborg, Sweden
Linkoping, Sweden
Stockholm, Sweden
United Kingdom
London, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01484275    
Obsolete Identifiers: NCT01563666
Other Study ID Numbers: CR100755
CNTO328SMM2001 ( Other Identifier: Janssen Research & Development, LLC )
2011-001735-22 ( EudraCT Number )
First Posted: December 2, 2011    Key Record Dates
Results First Posted: January 27, 2020
Last Update Posted: January 27, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Research & Development, LLC:
High-risk smoldering multiple myeloma
Multiple myeloma
Siltuximab
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Hypergammaglobulinemia
Siltuximab
Antineoplastic Agents