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

NCT ID: NCT01484275

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-01
• Study Completion Date: 2019-08-21

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.

Conditions

High-risk Smoldering Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Siltuximab

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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 Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Chicago, Illinois, United States

Rockville, Maryland, United States

Detroit, Michigan, United States

New York, New York, United States

Kittanning, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Greenville, South Carolina, United States

Dallas, Texas, United States

Camperdown, , Australia

East Melbourne, , Australia

Randwick, , Australia

Antwerp, , Belgium

Brussels, , Belgium

Ghent, , Belgium

Dijon, , France

Nantes, , France

Tours, , France

Villejuif, , France

Berlin, , Germany

Hamburg, , Germany

Heidelberg, , Germany

Athens, , Greece

Ashkelon, , Israel

Jerusalem, , Israel

Nahariya, , Israel

Netanya, , Israel

Petah Tikva, , Israel

Tel Aviv, , Israel

Daejeon, , South Korea

Seoul, , South Korea

Barcelona, , Spain

Barcleona, , Spain

Madrid, , Spain

Salamanca, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Linköping, , Sweden

Stockholm, , Sweden

London, , United Kingdom

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; France; Germany; Greece; Israel; South Korea; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30890552 (View on PubMed)

Other Identifiers

CNTO328SMM2001

Identifier Type: OTHER

Identifier Source: secondary_id

2011-001735-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100755

Identifier Type: -

Identifier Source: org_study_id

NCT01563666

Identifier Type: -

Identifier Source: nct_alias