What side effects are associated with this type of intervention?

Common treatments for Large Granular Lymphocyte Leukemia (LGLL) include immunomodulatory drugs and monoclonal antibodies, such as rituximab. Side effects of these treatments can include infusion reactions, which may be severe, especially during the first cycle, and hematologic adverse effects like neutropenia and anemia. Specific to IL-6 inhibitors like Siltuximab, potential side effects may include increased risk of infections, liver enzyme abnormalities, and gastrointestinal symptoms. It is important to monitor patients closely for these adverse effects during treatment.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for the treatment of Large Granular Lymphocyte Leukemia (LGLL) in the provided context. Siltuximab, which targets IL-6, is currently being studied for its safety and effectiveness in treating LGLL. Broadly, treatments for LGLL often involve immunosuppressive therapies, but specific FDA-approved drugs for this condition were not detailed in the context.

What other types of research exist?

Promising novel alternatives to Siltuximab for LGLL patients in 2024 may include other cytokine inhibitors, such as those targeting IL-23 or IL-12, and advanced immunotherapies like CAR T-cell therapies or bispecific antibodies. These approaches have shown efficacy in other hematologic malignancies and could be considered for LGLL treatment.

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Monoclonal Antibodies

Siltuximab for Leukemia

Q: What is the mechanism of action of this treatment?

Siltuximab, an IL-6 inhibitor, works by blocking the activity of interleukin-6, a cytokine involved in inflammation and the proliferation of malignant cells in Large Granular Lymphocyte Leukemia (LGLL). This inhibition can reduce the survival and growth of leukemic cells. Other common treatments for LGLL include immunosuppressive therapies like methotrexate and cyclosporine, which reduce the activity of the immune system to control the overproduction of large granular lymphocytes. Understanding these mechanisms is crucial for LGLL patients as it helps in selecting targeted therapies that can effectively manage the disease by addressing its underlying biological processes.

Phase < 1

Recruiting

Led By Lubomir Sokol, MD, PhD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Meet the diagnosis criteria of LGLL as specified

Must not have

Any active infection requiring systemic therapy, including viral infections such as HIV, Hepatitis B, and/or Hepatitis C

Has coexisting myelodysplastic syndrome (MDS)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 months

Awards & highlights

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects of siltuximab may include allergic reactions specific to the drug itself. Since detailed side effects are not provided here, they typically range from mild reactions at the infusion site to more serious systemic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of my waking hours.

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I have been diagnosed with LGL leukemia.

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My liver disease is mild to moderate.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have been diagnosed with myelodysplastic syndrome.

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I am currently taking methotrexate, cyclophosphamide, or cyclosporine.

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I have other cancers that are not considered cured, except for certain types.

Select...

I have not had a live vaccine within 30 days before starting the study drug and won't get one during the study or for 3 months after.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Response Rate

Secondary study objectives

Complete Response Rate (CR)

Duration of Complete Response

Duration of Complete Response with Normalization of PB LGL Count

+4 more

Side effects data

From 2021 Phase 3 trial • 342 Patients • NCT04330638

22%

Constipation

16%

Lung infection

Hyperglycaemia

Hypertriglyceridaemia

Hypertension

Atrial fibrillation

Neutrophil count decreased

Platelet count decreased

Nausea

Other

Bacteraemia

Sepsis

Cough

Rash maculo-papular

Multi-organ failure

Aspiration

Pneumothorax

Lower gastrointestinal haemorrhage

Hypotension

Alanine aminotransferase increased

Delirium

Diarrhoea

Gastroparesis

Hypokalaemia

Laryngeal stenosis

Respiratory failure

Stroke

Urinary tract infection

100%

80%

60%

40%

20%

Study treatment Arm

Anakinra + Tocilizumab

Anakinra

Siltuximab

Anakinra + Siltuximab

Tocilizumab

Usual Care

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups

Experimental Treatment

Group I: SiltuximabExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Siltuximab

FDA approved

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Siltuximab, an IL-6 inhibitor, works by blocking the activity of interleukin-6, a cytokine involved in inflammation and the proliferation of malignant cells in Large Granular Lymphocyte Leukemia (LGLL). This inhibition can reduce the survival and growth of leukemic cells. Other common treatments for LGLL include immunosuppressive therapies like methotrexate and cyclosporine, which reduce the activity of the immune system to control the overproduction of large granular lymphocytes. Understanding these mechanisms is crucial for LGLL patients as it helps in selecting targeted therapies that can effectively manage the disease by addressing its underlying biological processes.

Activity of lenalidomide in mantle cell lymphoma can be explained by NK cell-mediated cytotoxicity.