This phase II trial studies how well anakinra works in preventing severe decreased brain function (neurotoxicity), a dangerous condition called cytokine release syndrome (CRS) caused by CAR-T cells. T cells (a type of immune cells) are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added in the laboratory. The special receptor is called a chimeric antigen receptor (CAR) and this type of modified T cells are called CAR-T cells. Cytokines are proteins that control body’s inflammatory response. In CRS, a large amount of cytokines is released into the blood, which may cause changes in blood pressure and heartbeat, flu-like symptoms (nausea, fever, and chills), and/or affect the way lungs/liver/kidneys work. CAR-T cell therapy may also cause brain-related symptoms (neurotoxicity), such as dizziness, weakness, confusion, difficulty speaking, and/or possible paralysis, and/or coma. Anakinra works by blocking the inflammatory cytokine, called IL-1 (interleukin-1) that is released into the blood during or shortly after CAR-T cell therapy and causes an inflammatory (swelling) reaction. Anakinra may prevent or reverse the severe side effects of CAR-T cell therapy.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04148430.
PRIMARY OBJECTIVE:
I. To determine the rate of severe (i.e. >= grade 3 or any grade seizure) neurotoxicities within the first 4 weeks of treatment with prophylactic use of anakinra in patients receiving CD19- specific chimeric antigen receptor (CAR) T cells.
SECONDARY OBJECTIVES:
I. To assess the rate of severe (i.e. >= grade 3) cytokine release syndrome (CRS).
II. To assess the rate of all grades CRS and neurotoxicities.
III. To assess the rate of tocilizumab and corticosteroid use to manage CRS and/or neurotoxicities.
IV. To assess the rate of severe infections.
V. To assess the rate of overall response rates.
VI. To assess the serum and cerebrospinal fluid (CSF) cytokine profiles at baseline and post-anakinra.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive anakinra subcutaneously (SC) every 12 hours starting on day 2 of CAR-T cell infusion, or after 2 consecutive documented fevers of >= 38.5 degrees Celsius. Treatment with anakinra continues for 10 days in the absence of a fever, or until the resolution of fever.
COHORT II: Patients receive anakinra SC daily on day 0 2-3 hours post CAR-T cell infusion, every 12 hours after 1 consecutive documented fevers of >= 38.5 degrees Celsius, every 6 hours after 2 consecutive documented fevers of >= 38.5 degrees Celsius, and continuing for a minimum of 7 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 3 months and 6 months after CAR T cell infusion.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorJae Park
