Siltuximab for Leukemia

Overseen By Ning Dong, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Methotrexate, Cyclophosphamide, Cyclosporine

Disqualifiers: Active infection, MDS, 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: Unknown

Duration: 18-36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests siltuximab, a medication, to determine its safety and effectiveness in treating large granular lymphocytic leukemia (LGLL), a type of blood cancer. Participants will receive siltuximab every three weeks for up to 36 weeks to evaluate its impact on the disease. Eligible participants have been diagnosed with LGLL and experience issues like frequent infections or severe anemia that require treatment. The study aims to discover if siltuximab can improve these conditions. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, if you are currently receiving therapy, you must stop taking your medications for at least 30 days or 5 elimination half-lives, whichever is longer, before starting the study drug.

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

Research has shown that siltuximab has been tested for various conditions and appears safe. In one study, patients with idiopathic multicentric Castleman disease received siltuximab, which helped them live longer over three years. Another study found siltuximab safe when combined with another drug, showing positive early results for patients with a type of prostate cancer.

Siltuximab has also been used to treat immune system-related issues, proving safe and effective for these uses as well. Although these studies do not specifically focus on large granular lymphocytic leukemia (the type of leukemia in this trial), they suggest that siltuximab is generally well-tolerated in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Unlike traditional leukemia treatments that often rely on chemotherapy to kill rapidly dividing cells, Siltuximab works by targeting and neutralizing a specific protein called IL-6, which plays a role in inflammation and cancer growth. This targeted approach could potentially lead to fewer side effects compared to standard chemotherapy. Researchers are particularly excited about Siltuximab because it offers a new mechanism of action and could be a promising alternative for patients who do not respond well to existing therapies.

What evidence suggests that siltuximab might be an effective treatment for leukemia?

Research has shown that siltuximab effectively treats multicentric Castleman disease. In one study, 55.3% of patients had a complete response, and 15.8% had a partial response, indicating many patients experienced positive results. Another study found that 78% of patients showed improvement in their condition. In this trial, researchers are testing siltuximab for large granular lymphocytic leukemia (LGLL). Its success with similar diseases suggests it might work here too. The evidence supports the potential for siltuximab to help patients with LGLL, but more research is needed to confirm this. ^{1 6 7 8 9}

Who Is on the Research Team?

Lubomir Sokol, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults diagnosed with large granular lymphocytic leukemia (LGLL) who are willing to follow study procedures. Eligible participants can be new or previously treated for LGLL, must have certain blood cell counts or symptoms like severe neutropenia, recurrent infections, anemia, or thrombocytopenia. They should not have other active cancers (with some exceptions), coexisting conditions that could affect the trial's outcome, and must agree to contraception use.

Inclusion Criteria

For females of reproductive potential: use of highly effective contraception as specified

Provision of signed and dated informed consent form

Creatinine clearance (CLCr) ≥15 mL/min

Exclusion Criteria

Known severe allergic reactions to siltuximab

Pregnancy or lactation

I do not have any infections needing treatment through my bloodstream.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Siltuximab will be given every 3 weeks for between 18 and 36 weeks

18-36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 months

What Are the Treatments Tested in This Trial?

Interventions

• Siltuximab

Trial Overview The trial is testing the safety and effectiveness of siltuximab in treating LGLL. Participants will receive this medication and their response will be monitored to determine if it helps manage their condition better than existing treatments.

How Is the Trial Designed?

Group I: Siltuximab Experimental Treatment 1 Intervention

Siltuximab will be given every 3 weeks, for between 18 and 36 weeks

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

EUSA Pharma, Inc.

Industry Sponsor

Trials

6

Recruited

1,300+

Published Research Related to This Trial

Siltuximab, when combined with docetaxel, was found to be safe for patients with castration-resistant prostate cancer (CRPC), with only a few cases of dose-limiting toxicity reported among 39 patients in a phase 1 study.

The combination treatment showed promising efficacy, with 62% of patients achieving a significant decline in PSA levels, indicating a potential therapeutic benefit for CRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of a chimeric monoclonal antibody against interleukin-6, siltuximab, combined with docetaxel in patients with metastatic castration-resistant prostate cancer. Hudes, G., Tagawa, ST., Whang, YE., et al.[2021]

Siltuximab is the first approved treatment for multicentric Castleman's disease (MCD) in both the US and EU, highlighting its significance in addressing this rare condition.

The drug was approved through expedited processes, including the FDA's priority review and the EU's accelerated assessment, indicating its potential effectiveness and the urgent need for treatment options in MCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siltuximab: first global approval. Markham, A., Patel, T.[2021]

In a retrospective case series of 13 patients with Sézary syndrome, brentuximab vedotin demonstrated a global response rate of 38%, with notable efficacy in blood (63% response) and lymph nodes (50% response), suggesting it may be a viable treatment option for this challenging condition.

The treatment was generally well-tolerated, with manageable side effects such as peripheral neuropathy, which resolved in some cases, indicating that brentuximab vedotin could provide a safer alternative for patients with refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome. Lewis, DJ., Haun, PL., Samimi, SS., et al.[2021]

Siltuximab effectively blocks the IL-6/Stat3 signaling pathway in ovarian epithelial carcinoma, leading to reduced levels of phosphorylated Stat3 and anti-apoptotic proteins, which are often associated with cancer cell survival.

The treatment with siltuximab enhances the sensitivity of ovarian cancer cells to paclitaxel, significantly lowering the concentration needed to induce cell death, suggesting it may help overcome drug resistance in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of siltuximab on the interleukin-6/Stat3 signaling pathway in ovarian cancer]. Guo, YQ., Lu, P., Duan, ZF., et al.[2017]

Siltuximab was approved by the FDA for treating multicentric Castleman disease (MCD) in HIV-negative and HHV-8-negative patients, based on a randomized trial with 79 patients showing a significant response rate; 34% of those treated with siltuximab achieved a durable tumor and symptomatic response compared to none in the placebo group.

The treatment was generally well-tolerated, with common side effects including pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infections occurring in more than 10% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. Deisseroth, A., Ko, CW., Nie, L., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11526577/

Siltuximab in Idiopathic Multicentric Castleman Disease The overall response to siltuximab was 71.1%, with 55.3% of patients achieving a complete response, and 15.8% a partial response. The estimated ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05316116

Siltuximab in Large Granular Lymphocytic Leukemia (LGLL) The purpose of the study is to evaluate the safety and effectiveness of siltuximab for participants being treated for large granular lymphocytic leukemia ...

3. withpower.com withpower.com/trial/early-phase-1-leukemia-2-2022-f54f5

Siltuximab for Leukemia · Info for Participants Siltuximab has been shown to be effective in treating multicentric Castleman disease (MCD), where it helped 34% of patients achieve a significant response ...

4. 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 ...

5. southcarolinablues.com southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/siltuximab-sylvant/

Siltuximab (Sylvant) A total of 18 (78%) of 23 patients (95% confidence intervals [CI]: 56% to 93%) achieved CBR and 12 patients (52%) demonstrated objective tumor response. All 11 ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e19586

Post hoc analysis of a long-term safety extension study Disease control was observed in 31 of the 33 patients (93.9%) at their last on-study assessment (complete response [CR] in 9 [27.3%]).

7. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00638-3

Siltuximab for the treatment of early complications after ... Siltuximab directly binds interleukin-6 (IL-6) and may be safe and effective as first-line therapy for CRS or ICANS.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023013915

TCL-263 A Pilot Study of Siltuximab in Large Granular ... This is a single-arm, single-center, open-label study evaluating the safety and efficacy of siltuximab in LGLL (NCT05316116).

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

Siltuximab (Sylvant) - Medical Clinical Policy Bulletins The authors concluded that these results suggested that siltuximab in combination with docetaxel was safe and showed preliminary efficacy in patients with CRPC ...