The purpose of this study is to examine the safety, efficacy and feasibility of the use of one standard dose of siltuximab prior to teclistamab infusion. Siltuximab is an investigational (experimental) drug that works by binding directly to human interleukin-6 (IL-6). IL-6 is a cytokine; these are products that are secreted by certain cells of the immune system and effect other cells in participant's body. IL-6 regulates immune, inflammatory and metabolic processes. Siltuximab has already been tested and approved for use by the FDA in participants with a condition called multicentric Castleman's disease, which is a lymphoproliferative disorder. This study is being conducted to investigate if administration of a single dose of siltuximab will reduce the rates of and severity of Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) in participants prior to teclistamab administration. CRS and ICANS are adverse effects commonly experienced by participants being treated with teclistamab that are related to inflammation in the body. Siltuximab is experimental because it is not approved by the Food and Drug Administration (FDA) for prophylactic use prior to administration of teclistamab infusion.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are clinically relevant toxicities of bsAbs and other T cell redirecting therapies. The armamentarium of immunotherapeutic approaches is expected to grow at exponential rates in the upcoming years, with an expansion of the diseases treated with this modality. While the risk of CRS and ICANS is limited with most bsAbs(bispecific antibodies), these side effects can prevent a more widespread adoption of these therapies and impede their use in participants for whom access to tertiary or quaternary medical centers is limited. The development of strategies that prevent CRS and ICANS occurring after bispecific antibodies can increase the prescription of these effective immunotherapies, in particular for participants for whom access to care is limited. Siltuximab is a chimeric murine antibody that binds directly to IL-6 and has been used effectively in the treatment of CRS, with guidelines recommending its use in CRS cases refractory to tocilizumab. Study hypothesis is that, through direct binding of IL-6, siltuximab can overcome the risk of increased IL-6 - mediated ICANS by decreasing the available IL-6 for blood brain barrier passage and by facilitating clearance of IL-6 through IL-6 receptor-mediated mechanisms. Based on this rationale, a phase II study investigating the use of siltuximab for CRS and ICANS prophylaxis prior to therapy with the BCMAxCD3 bispecific antibody teclistamab. This study will examine the safety, efficacy and feasibility of the use of standard doses of siltuximab prior to teclistamab infusion and will determine the rates of all grades as well as grade 2 or higher CRS and ICANS in participants given prophylaxis prior to teclistamab, which has well defined rates of CRS and ICANS. This will allow for a preliminary assessment of the efficacy of siltuximab as preventive measure against CRS and ICANS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Siltuximab is an investigational (experimental) drug that works by binding directly to human interleukin-6 (IL-6). IL-6 is a cytokine; these are products that are secreted by certain cells of the immune system and effect other cells in participant's body. IL-6 regulates immune, inflammatory and metabolic processes. Siltuximab has already been tested and approved for use by the FDA in participants with a condition called multicentric Castleman's disease, which is a disorder of the lymphatic system
Teclistamab is a FDA-approved drug for the treatment of advanced MM after 4 lines of therapy.
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio
Cleveland, Ohio, United States
Change in CRS Rate
ASTCT criteria will be used to report CRS
Time frame: First two 22-day cycles after treatment initiation or until death, whichever occurs first.
Safety assessment of a single dose of siltuximab as CRS prophylaxis
Adverse events graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: From the start of the infusion of the first dose of siltuximab until 22 days.
Incidence of grade ≥ 2 cytokine release syndrome after siltuximab prophylaxis
Response to siltuximab prophylaxis will be measured by incidence of all grade CRS and grade ≥ 2 CRS. Grading will be done according to the ASTCT consensus criteria
Time frame: First two 22-day cycles after treatment initiation or until death, whichever occurs first.
Incidence of all grade ICANS after siltuximab prophylaxis
Grading will be done according to the ASTCT consensus criteria
Time frame: First two 22-day cycles after treatment initiation or until death, whichever occurs first.
Incidence of adverse events after siltuximab prophylaxis
Adverse events will be graded according to NCI CTCAE Version 5.0
Time frame: First two 22-day cycles after treatment initiation or until death, whichever occurs first
Overall response rate
Survival rates will be calculated using Kaplan Meier method
Time frame: 6 months after treatment initiation or until disease progression, whichever comes first.
Progression free survival
Survival rates will be calculated using Kaplan Meier method
Time frame: 6 months after treatment initiation or until disease progression, whichever comes first.
Overall survival
Survival rates will be calculated using Kaplan Meier method
Time frame: 6 months after treatment initiation or until disease progression, whichever comes first.
Hospitalization rates
Percentage as measured by Karnofsky Performance Scale to monitor hospitalization rates from 0 to 100, where 0 being death and 100 being normal, no complaints, no evidence of disease
Time frame: First two 22-day cycles after treatment initiation or until death, whichever occurs first
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