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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Undergo blood sample collection
Undergo CT scan
Undergo PET scan
Given IV
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Frequency and nature of adverse events associated with siltuximab prophylaxis prior to CD19 directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) cell therapy
Adverse events (AEs) will be described and classified per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 guidelines. The maximum grade of each type of toxicity will be extracted for each patient, and frequency counts will be tabulated to determine toxicity patterns, especially for grade 3 or above adverse events. The AE data associated with prophylaxis will be summarize for every patient: for patients receiving siltuximab only as prophylaxis, all AEs occur during the 30-day dose limiting toxicity observation period will be considered; for patients receiving siltuximab both as prophylaxis and as treatment, only the AEs occur before the treatment start will be considered for the primary endpoint.
Time frame: Up to 30 days after the last infusion of siltuximab
Frequency and nature of adverse events associated with siltuximab treatment of cytokine release syndrome (CRS) and/or immune effector cell associated neurotoxicity syndrome (ICANS)
AEs will be described and classified per the NCI CTCAE v5.0 guidelines. The maximum grade of each type of toxicity will be extracted for each patient, and frequency counts will be tabulated to determine toxicity patterns, especially for grade 3 or above adverse events. AEs post treatment start will be summarized for the secondary endpoint.
Time frame: Up to 30 days after the last infusion of siltuximab
Incidence of all grade CRS and grade >= 3 CRS
According to American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.
Time frame: Up to 30 days after the last infusion of siltuximab
Incidence of all grade ICANS and grade >= 3 ICANS
According to ASTCT consensus grading criteria.
Time frame: Up to 30 days after the last infusion of siltuximab
Percentage of participants who achieve resolution of CRS
Defined as absence of symptoms leading to diagnosis of CRS.
Time frame: At 24 hours from treatment
Objective response rate (complete response [CR] + partial response [PR])
The ORR (CR + PR) will be calculated at the initial 30 day imaging assessment and 95% confidence interval computed.
Time frame: At day 30 following CD19.CAR-T cell therapy
Progression free survival
Will be estimated using the Kaplan-Meier method.
Time frame: From the date of treatment initiation to date of progression or death, whichever occurs first, assessed up to 1 year
Overall survival
Will be estimated using the Kaplan-Meier method.
Time frame: From date of treatment initiation to date of death due to all causes, assessed up to 1 year
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