Clinical trial NCT01484275: A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients With High-risk Smoldering Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: High-risk Smoldering Multiple Myeloma
Keywords: High-risk smoldering multiple myeloma
Multiple myeloma
Siltuximab
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-12-02
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: One-Year Progression-Free Survival (PFS) Rate
timeFrame: Up to 1 Year
Secondary outcomes:
measure: Progressive Disease Indicator Rate (PDIR) at 6 Months
timeFrame: At 6 Months
measure: Progression-Free Survival
timeFrame: Up to 4.7 Years
measure: Percentage of Participants With Serum M-protein Response
timeFrame: Up to 4.7 Years
measure: Time to Worsening in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scale Score
timeFrame: Up to 4.7 Years
measure: Time to Worsening in the Brief Pain Inventory (BPI) Worst Item Scores
timeFrame: Up to 4.7 Years
measure: Number of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features
timeFrame: Up to 4.7 Years
measure: Number of Participants With Best Response to First Subsequent Multiple Myeloma Treatment
timeFrame: Up to 4.7 Years
measure: Overall Survival (OS)
timeFrame: Up to 4.7 Years
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Rockville
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Kittanning
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Camperdown
country: Australia
city: East Melbourne
country: Australia
city: Randwick
country: Australia
city: Antwerpen
country: Belgium
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Dijon
country: France
city: Nantes Cedex 1
country: France
city: Tours
country: France
city: Villejuif
country: France
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Athens
country: Greece
city: Ashkelon
country: Israel
city: Jerusalem
country: Israel
city: Nahariya
country: Israel
city: Netanya
country: Israel
city: Petach Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Daejeon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Barcelona
country: Spain
city: Barcleona
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Linkoping
country: Sweden
city: Stockholm
country: Sweden
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.