This phase II trial studies the side effects and best dose of anakinra and to see how well it works in reducing side effects (toxicity) associated with a CAR-T cell treatment called axicabtagene ciloleucel in patients with large B-cell lymphoma that has come back (relapsed) or has not responded to treatment (refractory). Anakinra is a drug typically used to treat rheumatoid arthritis but may also help in reducing CAR-T cell therapy toxicity. Giving anakinra in combination with axicabtagene ciloleucel may help control relapsed or refractory large B-cell lymphoma.
PRIMARY OBJECTIVE: I. To assess safety and tolerability of anakinra in reducing incidence of cytokine release syndrome (CRS) within 30 days after infusion of chimeric antigen receptor (CAR) T cells in subjects with relapsed or refractory large B-cell lymphoma. SECONDARY OBJECTIVES: I. To determine incidence of all grades and duration of both CRS and immune-cell associated neurotoxicity syndrome (ICANS). II. To determine the complete response rate (CRR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To determine the effects of anakinra on the cytokine and chemokine profile in peripheral blood after CAR-T therapy. II. To determine the effects of anakinra on the expansion and persistence of CAR T cells. III. To correlate baseline characteristics with toxicity, response and survival after anakinra combined with CAR-T therapy. OUTLINE: This is a dose-escalation study of anakinra. Patients receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive axicabtagene ciloleucel IV over 30 minutes or less on day 0 and anakinra subcutaneously (SC) on days 0-6 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 2 and 4 weeks, and then at 2, 3, 6, 9, 12, 18, and 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Given SC
Given IV
Given IV
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
Incidence of Any Grade Cytokine Release Syndrome (CRS)
Will be tabulated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version (v)5.0. CRS will be assessed by both Lee 2014 criteria as well as American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading system.
Time frame: Within 30 days after infusion of CAR T cells
Incidence of Different Grades and Duration of Both CRS and Immune Cell-associated Neurotoxicity Syndrome (ICANS)
Will be tabulated according to the NCI CTCAE v5.0. CRS will be assessed by both Lee 2014 criteria as well as ASTCT Consensus Grading system. ICANS will be assessed by both CTCAE v5.0 as well as ASTCT Consensus Grading system.
Time frame: 30 days
Overall Response Rate
Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma.
Time frame: Up to 24 months
Complete Response Rate
Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma.
Time frame: Up to 24 months
Progression Free Survival
Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma. Will be estimated using the method of Kaplan and Meier.
Time frame: From the start of treatment to disease progression or death due to any cause whichever happened first, assessed up to 24 months
Overall Survival
Will be assessed using the Cheson 2014 Lugano Classification response criteria for malignant lymphoma. Will be estimated using the method of Kaplan and Meier.
Time frame: From the start of treatment to death due to any cause, assessed up to 24 months
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