Siltuximab for the Prevention of CAR T Cell Related Cytokine Release Syndrome in Patients With CD19 Positive Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma Clinical Trial

Official title: Phase I Study of Cytokine Release Syndrome Prophylaxis and Treatment With Siltuximab

Status Active, not recruiting

Clinical Trial Summary

This phase I trial tests the safety and side effects of siltuximab in preventing CAR T cell therapy related cytokine release syndrome in patients with CD19 positive non-Hodgkin lymphoma. Several of the major complications of CD19 directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) include cytokine release syndrome (CRS, a complication of a highly active immune system seen with some cancer treatments including CD19.CAR-T cell therapy) and immune effector cell therapy associated neurotoxicity (ICANS, neurologic complications related to an activated immune system seen with immunotherapy and CD19.CAR-T cell therapy). Siltuximab is a chimeric (having parts of different origins) murine (from mice) antibody that binds directly to IL-6 (a cytokine/ body chemical causing toxicities) and allows for its clearance. IL-6 is known to increase in a patient's blood after CD19.CAR-T cell infusion and has been associated with development of CRS and ICANS. Giving siltuximab prior to CD19.CAR-T cell therapy may help reduce CRS and/or ICANS after therapy.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the safety of siltuximab when given prior to CD19.CAR-T cells for prevention of cytokine release syndrome associated CAR-T cell therapy.

SECONDARY OBJECTIVES:

I. To describe the safety profile of siltuximab as first line treatment of new onset grade >= 2 cytokine release syndrome (CRS).

II. To estimate the incidence of all-grade CRS and grade >= 3 CRS after CAR-T cell therapy with siltuximab prophylaxis.

III. To estimate the incidence of all grade immune effector cell associated neurotoxicity syndrome (ICANS) and grade >= 3 ICANS after CAR-T cell therapy with siltuximab prophylaxis.

IV. To describe the response rates of grade >= 2 CRS to treatment with a second dose of siltuximab.

V. To describe the disease response rates of lymphoma patients after CD19.CAR-T cell therapy with siltuximab prophylaxis.

VI. To estimate the progression free survival (PFS) in subjects treated with CD19.CAR-T cell therapy with siltuximab prophylaxis.

VII. To estimate the overall survival (OS) in subjects treated with CD19.CAR-T cell therapy with siltuximab prophylaxis.

EXPLORATORY OBJECTIVES:

I. To describe CD19.CAR-T cell expansion and persistence following treatment with siltuximab prophylaxis.

II. To describe changes in plasma cytokine concentrations in patients treated with CD19.CAR-T cells with prophylactic siltuximab.

III. To describe changes in peripheral blood immunophenotypes in patients treated with CD19.CAR-T cells with prophylactic siltuximab.

IV. To examine the role of complement activation on development and persistence of ICANS.

V. To examine the correlation between apheresis product, infusional CAR-T product, and pre-lymphodepletion immunophenotypes with CRS/ICANS and CD19.CAR- T clinical response.

OUTLINE:

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

Related Conditions & MeSH terms

• Cytokine Release Syndrome
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

• NCT number: NCT05665725
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 31, 2023
• Completion date: December 31, 2025