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

Janssen Research & Development, LLC85 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

High-risk Smoldering Multiple Myeloma

Interventions

SiltuximabDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (40)

Unnamed facility

Chicago, Illinois, United States

Outcomes

Primary Outcomes

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).

Time frame: Up to 1 Year

Secondary Outcomes

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).

Time frame: At 6 Months

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).

Data from ClinicalTrials.gov

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