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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing siltuximab, a drug that blocks a protein to help treat a rare blood cancer called LGLL. The goal is to see if it is safe and effective for these patients. Siltuximab has shown promise in treating multiple myeloma, B-cell non-Hodgkin lymphoma, and Castleman disease, leading to its approval for Castleman disease by the FDA.

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.

What data supports the effectiveness of the drug Siltuximab for treating leukemia?

Siltuximab has been shown to be effective in treating multicentric Castleman disease (MCD), where it helped 34% of patients achieve a significant response compared to none in the placebo group. This suggests that Siltuximab, which targets a protein involved in inflammation and cancer growth, may have potential benefits for other conditions like leukemia. ^{1 2 3 4 5}

How is the drug Siltuximab unique for treating leukemia?

Siltuximab is unique because it targets interleukin-6 (IL-6), a protein that plays a role in inflammation and cancer growth, which is different from many other leukemia treatments that focus on different pathways or mechanisms. ^{6 7 8 9 10}

Research Team

Ning Dong, MD, MS

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Siltuximab (CNTO 328): a promising option for human malignancies. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. [2017]

3. China pubmed.ncbi.nlm.nih.gov

[Effects of siltuximab on the interleukin-6/Stat3 signaling pathway in ovarian cancer]. [2017]

4. United States 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. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Siltuximab: first global approval. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mogamulizumab by patient baseline blood tumour burden: a post hoc analysis of the MAVORIC trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Multicentric EORTC retrospective study shows efficacy of brentuximab vedotin in patients who have mycosis fungoides and Sézary syndrome with variable CD30 positivity. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of filgotinib for Japanese patients with RA and inadequate response to MTX: FINCH 1 52-week results and FINCH 4 48-week results. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Therapeutic potential of spleen tyrosine kinase inhibition for treating high-risk precursor B cell acute lymphoblastic leukemia. [2021]