Siltuximab + Teclistamab for Multiple Myeloma
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests whether a new combination of treatments can benefit people with multiple myeloma, a type of blood cancer. Researchers aim to determine if administering siltuximab (also known as Sylvant) before teclistamab can reduce inflammation-related side effects. The goal is to make the treatment safer and more effective. Individuals who have tried at least four other treatments for multiple myeloma but still have active disease might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in multiple myeloma treatment.
Do I need to stop my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that siltuximab is generally well-tolerated. Previous studies found that about 60% of patients experienced significant side effects, such as high blood pressure. Infections were also common, affecting around 57% of patients, with some being severe. These side effects are important to consider, but careful monitoring makes the treatment manageable.
The FDA has already approved siltuximab for treating multicentric Castleman's disease, indicating its safety is well-understood for that purpose. However, in this trial, its use is experimental because it is administered before another drug, teclistamab, to determine if it can help reduce some of the side effects of that drug.12345Why are researchers excited about this study treatment for multiple myeloma?
Unlike the standard treatments for multiple myeloma, which often include drugs like bortezomib, lenalidomide, and dexamethasone, the combination of siltuximab and teclistamab offers a fresh approach by targeting different pathways. Siltuximab is unique because it is an anti-IL-6 monoclonal antibody, which helps manage cytokine release syndrome (CRS), a common and potentially severe side effect of many myeloma treatments. Teclistamab, on the other hand, is a bispecific antibody that engages both T cells and myeloma cells, aiming to enhance the immune system's ability to attack cancer more directly. Researchers are excited about this combination because it not only potentially reduces side effects but also utilizes the immune system in a novel way to combat the disease.
What evidence suggests that this treatment might be an effective treatment for multiple myeloma?
Research has shown that siltuximab attaches to a protein called interleukin-6 (IL-6), which plays a role in the body's immune and inflammation responses. This protein often contributes to conditions where the immune system overreacts. Siltuximab is already approved to treat multicentric Castleman's disease, demonstrating its effectiveness in managing diseases with high IL-6 activity. In studies on multiple myeloma, siltuximab showed potential to slow the disease, although it didn't always extend survival when combined with other treatments. In this trial, participants will receive siltuximab before teclistamab, with the hope that siltuximab can reduce inflammation-related side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). By calming the immune response, it may make teclistamab treatment safer.56789
Who Is on the Research Team?
Jack Khouri, MD
Principal Investigator
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio
Are You a Good Fit for This Trial?
This trial is for individuals with relapsed or refractory multiple myeloma, who may experience severe inflammatory reactions (CRS and ICANS) from teclistamab treatment. Specific eligibility criteria are not provided, but typically include factors like age, disease stage, prior treatments, and overall health status.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive a single dose of prophylactic siltuximab prior to teclistamab infusion, followed by monitoring for CRS and ICANS
Follow-up
Participants are monitored for safety and effectiveness after treatment, including incidence of CRS and ICANS
What Are the Treatments Tested in This Trial?
Interventions
- Siltuximab
Trial Overview
The study tests if a dose of siltuximab before teclistamab infusion can reduce the rates and severity of CRS and ICANS in patients. Siltuximab targets IL-6, a cytokine involved in inflammation. It's approved for Castleman's disease but experimental for this prophylactic use.
How Is the Trial Designed?
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Treatment groups
Experimental Treatment
Participants will receive a single dose of prophylactic siltuximab, 11 mg/kg, 2 hours prior to the administration of the first dose of teclistamab on day 1. There is no planned dose escalation of siltuximab, and teclistamab dosing will be done following the standard planned ramp-up mentioned below. Participants will be hospitalized for 9 days according to teclistamab package insert and Cleveland Clinic institutional practice. Participants will be followed for the incidence of CRS and ICANS for the first two 22-day cycles of treatment.
Siltuximab is already approved in European Union, United States, Canada, Japan for the following indications:
- Multicentric Castleman's disease
- Multicentric Castleman's disease
- Multicentric Castleman's disease
- Multicentric Castleman's disease
Find a Clinic Near You
Who Is Running the Clinical Trial?
Case Comprehensive Cancer Center
Lead Sponsor
Jack Khouri
Lead Sponsor
Jack Khouri, MD
Lead Sponsor
Citations
Randomized, Double-Blind, Placebo-Controlled, ...
This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma.
NCT01266811 | A Phase 3 Study of Siltuximab or Placebo ...
Siltuximab is being developed to see if it may be useful in treating multiple myeloma, including multiple myeloma that has returned after (relapsed) or did not ...
A Phase 2, Randomized, Double-Blind, Placebo- ...
After a median follow-up of 29.2 months, there were 32.6% PFS events (14/43 pts) in the siltuximab group and 42.9% (18/42 pts) in the placebo ...
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aacrjournals.org
aacrjournals.org/clincancerres/article/25/13/3772/81594/Randomized-Double-Blind-Placebo-ControlledRandomized, Double-Blind, Placebo-Controlled, Multicenter ...
After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with ...
A phase 2, randomized, double-blind, placebo-controlled ...
The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or ...
siltuximab - accessdata.fda.gov
SYLVANT may cause infusion related reactions and anaphylaxis. Approximately 945 patients have been treated with SYLVANT in clinical trials. Of these, one ...
Long-term safety of siltuximab in patients with idiopathic ...
Siltuximab was well tolerated; however, adverse events of grade 3 or worse were reported in 36 (60%) of 60 patients with the most common being hypertension ( ...
An Efficacy and Safety Study of Siltuximab in Participants ...
The purpose of this study is to evaluate the safety and efficacy of siltuximab in participants with relapsed (the return of a disease or the ...
Siltuximab (Sylvant) - Medical Clinical Policy Bulletins
Infections occurred in 57 % of combination-treated patients, including greater than or equal to grade 3 infections in 18 %. The authors concluded that further ...
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