Siltuximab + Teclistamab for Multiple Myeloma

Overseen By Jack Khouri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: HIV/AIDS, Hepatitis B/C, CNS pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 44 days

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. ^{1 2 3 4 5}

Why 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. ^{5 6 7 8 9}

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

I am able to get out of my bed or chair and move around.

I agree to either not have sex or use birth control, and not donate sperm.

My blood counts meet the required levels for treatment.

Exclusion Criteria

Pregnant or breastfeeding women

Participants with history of severe hypersensitivity reaction to siltuximab or any of the excipients

Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of prophylactic siltuximab prior to teclistamab infusion, followed by monitoring for CRS and ICANS

44 days

Participants are hospitalized for 9 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of CRS and ICANS

6 months

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?

Group I: Siltuximab Experimental Treatment 2 Interventions

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:

Approved in European Union as Sylvant for:

• Multicentric Castleman's disease

Approved in United States as Sylvant for:

• Multicentric Castleman's disease

Approved in Canada as Sylvant for:

• Multicentric Castleman's disease

Approved in Japan as Sylvant for:

• Multicentric Castleman's disease

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Jack Khouri

Lead Sponsor

Trials

1

Jack Khouri, MD

Lead Sponsor

Trials

1

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30890552/

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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01266811

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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119836716

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 ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/25/13/3772/81594/Randomized-Double-Blind-Placebo-Controlled

Randomized, 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25294016/

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 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/125496s013lbl.pdf

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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32027862/

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 ( ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00402181

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 ...

9. aetna.com aetna.com/cpb/medical/data/800_899/0884.html

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 ...