Siltuximab for Non-Hodgkin's Lymphoma

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Timothy Voorhees

Must not be taking: Steroids

Disqualifiers: Active CNS involvement, HIV, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 30 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether siltuximab (Sylvant) can safely reduce complications from a specific cancer treatment for non-Hodgkin's lymphoma. The focus is on preventing cytokine release syndrome (CRS) and neurotoxicity, potential side effects of CAR T cell therapy, which uses altered blood cells to fight cancer. Siltuximab might help calm the immune response that causes these issues. People with non-Hodgkin's lymphoma who are candidates for CAR T cell therapy and experience frequent treatment-related issues might be suitable for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this potential new therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on daily corticosteroids at a dose greater than 10mg of prednisone, you may not be eligible to participate.

Is there any evidence suggesting that siltuximab is likely to be safe for humans?

Research shows that siltuximab is generally well-tolerated by patients. In a study with 254 patients taking only siltuximab, no unexpected safety issues arose. The most common side effects included rash, itching, and upper respiratory infections, affecting more than 10% of patients. Some patients also experienced weight gain and higher levels of uric acid, which can lead to gout.

In another study, serious side effects were less common. A small number of patients experienced fatigue and night sweats. Infusion reactions, or reactions to the drug entering the body, were infrequent and usually mild.

These findings suggest that siltuximab is safe based on previous research. Its FDA approval for other conditions further supports its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Siltuximab is unique because it targets a specific protein called interleukin-6 (IL-6), which plays a role in the growth of some cancer cells. Unlike the standard treatments for Non-Hodgkin's Lymphoma, such as chemotherapy and immunotherapy, siltuximab works by directly inhibiting IL-6, potentially reducing inflammation and slowing tumor growth. Researchers are excited about this treatment because it offers a novel approach that could enhance the effectiveness of existing therapies, like CAR-T cell therapy, and possibly improve outcomes for patients who have not responded well to current options.

What evidence suggests that siltuximab might be an effective treatment for preventing cytokine release syndrome in non-Hodgkin's lymphoma?

Research has shown that siltuximab, an antibody treatment, offers potential benefits for patients with B-cell non-Hodgkin lymphoma. In studies, many patients maintained stable disease, meaning their condition did not worsen, for over 11 weeks. In this trial, participants will receive siltuximab before CE19.CAR-T cell therapy. Siltuximab attaches to a protein called IL-6, which can trigger harmful immune reactions. By removing IL-6 from the body, it may reduce the risk of complications like cytokine release syndrome (CRS) and nerve damage, often seen with some cancer treatments. This suggests that siltuximab could be effective when combined with CAR T-cell therapy. ^{1 4 6 7 8}

Who Is on the Research Team?

Timothy J. Voorhees, MD, MSCR

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with CD19 positive non-Hodgkin lymphoma eligible for standard CAR-T cell therapy can join this trial. They must have certain blood and organ function levels, not be pregnant or breastfeeding, use contraception if of childbearing potential, and cannot have active central nervous system lymphoma or uncontrolled illnesses.

Inclusion Criteria

Aspartate aminotransferase (AST) =< 3.0 × ULN (obtained within 14 days prior to initiating study treatment)

I am eligible for a specific CAR-T cell therapy.

Hemoglobin >= 8.0 x 10^9/L (obtained within 14 days prior to initiating study treatment)

Exclusion Criteria

I do not have active brain conditions like epilepsy, severe strokes, or Parkinson's.

I had a severe reaction to my first siltuximab infusion.

Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drugs)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive siltuximab intravenously prior to CD19.CAR-T cell therapy and as clinically indicated on study

Up to 30 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and response rates

Up to 1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Siltuximab

Trial Overview The trial is testing siltuximab's ability to prevent cytokine release syndrome (CRS) and neurotoxicity in patients undergoing CAR-T cell therapy. Siltuximab is an antibody that targets IL-6, a body chemical linked to these side effects.

How Is the Trial Designed?

Group I: Treatment (siltuximab, biospecimen) Experimental Treatment 4 Interventions

Patients receive siltuximab IV prior to CE19.CAR-T cell therapy and as clinically indicated on study. Patients undergo CT scan or PET scan throughout the trial. Patients also undergo blood sample collection during screening and on study.

Who Is Running the Clinical Trial?

Timothy Voorhees

Lead Sponsor

Trials

3

Recruited

70+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5769562/

Impact of siltuximab on patient-related outcomes in ... The study concluded that siltuximab was associated with significantly better outcomes and that rituximab was no better than traditional ...

2. cdcn.org cdcn.org/wp-content/uploads/2024/08/3659.pdf

A Phase I, Open-Label Study of Siltuximab, an Anti–IL-6 ... This study evaluated the safety and pharmacoki- netics of siltuximab in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or ...

3. member.myhealthtoolkitex.com member.myhealthtoolkitex.com/web/public/brands/medicalpolicy/external-policies/siltuximab-sylvant/

Siltuximab (Sylvant) In part 2, stable disease (SD) (greater than or equal to 11 weeks) or better was achieved by 11 out of 17 (65%) 3 mg/kg treated patients (1 PR at approximately ...

4. withpower.com withpower.com/trial/phase-1-syndrome-7-2024-1ae72

Siltuximab + Epcoritamab for Non-Hodgkin's Lymphoma Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed a 63.1% overall response rate in 157 patients with relapsed or refractory large B-cell ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119618859

Long-Term Safety in a Phase 1 Study of Siltuximab (CNTO ... Phase 2 and 3 studies are ongoing to further evaluate the safety and efficacy of siltuximab in patients with multicentric Castleman's disease and in combination ...

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

Siltuximab (Sylvant) - Medical Clinical Policy Bulletins The most common adverse reactions (>10% of patients) were rash, pruritus, upper respiratory tract infection, increased weight, and hyperuricemia (EUSA Pharma, ...

7. sylvant.com sylvant.com/hcp/wp-content/uploads/sites/3/2024/09/23-RRD-0443-SYLVANT-NCCN-Guidelines-Update_DIGITAL_R1.pdf

SYLVANT® (siltuximab) Is Recommended by the NCCN as ... Lymphoma (Hodgkin and non-Hodgkin). Multiple myeloma. Primary lymph node ... Data from 254 patients treated with SYLVANT monotherapy forms the basis of the safety.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4745809/

A phase 2, open-label, multicenter study of the long-term ... The most commonly reported grade-≥3 AEs included fatigue (9%) and night sweats (8%); infusion reactions were relatively infrequent (8%) and generally of low ...