The goal of this clinical trial is to reduce the duration of ICANS and incidence of G3 or great ICANS in participants who receive axi-cel. The main questions the study aims to answer are: Efficacy of IT therapy to reduce high-grade ICANS in participants who receive axi-cel in NHL compared to historical experience.
This phase II trial tests how well giving intrathecal (IT) cytarabine and hydrocortisone works for the early treatment of immune effector cell associated neurotoxicity syndrome (ICANS) in patients undergoing chimeric antigen response (CAR) t cell therapy for the treatment of non Hodgkin Lymphoma that has come back after a period of improvement (recurrent) or that has not responded o previous treatment (refractory). CAR T-cell therapy can sometimes cause an overactive immune response and inflammation. This can cause a side effect called ICANS that affects the rain and may lead to symptoms such as confusion, difficulty speaking, or other neurological problems. Giving cytarabine and hydrocortisone directly into the fluid around the brain and spinal cord (called intrathecal treatment) may help lower the body's immune response and reduce inflammation. Giving IT cytarabine and hydrocortisone may be effective for early treatment of CANS in patients undergoing CAR T cell therapy for relapsed or refractory non Hodgkin Lymphoma.
Age ≥ 18 years
Diffuse large B-cell lymphoma (DLBCL)
Primary mediastinal large B-cell lymphoma (PMBCL)
Transformed follicular lymphoma (tFL)
Active HBV/HCV infection. See Inclusion Criteria 7 (HBV) and 8 (HCV) for requirements.
Patients with uncontrolled systemic infection despite appropriate antibiotics or other treatment.
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
History of platelet transfusion refractoriness or participant declining transfusion support (i.e. Jehovah's witness).
Single group
Therapeutic Hydrocortisone
Drug100 mg IT with onset of grade 1/2 ICANS
Cytarabine
Drug100 mg IT with onset of grade 1/2 ICANS
Dexamethasone
DrugIV 10mg
Methylprednisolone
Drug1g daily until adverse events resolves
Cyclophosphamide
DrugGiven as standard of care
Axicabtagene Ciloleucel
Biological/VaccineGiven as standard of care
Brexucabtagene Autoleucel
Biological/VaccineGiven as standard of care
Efficacy of IT therapy to reduce high-grade ICANS in participants who receive axi-cel in NHL compared to historical experience
Incidence of \> Grade 3 ICANS after IT therapy in subjects with grade 1-2 ICANS
Progression free survival
Will be analyzed using the Kaplan-Meier method to estimate the survival distribution.
Impact of IT therapy on CAR T toxicities
Incidence, grade, duration of CRS and ICANS
Adverse events from IT therapy
Incidence of AE resulting from IT therapy
Feasibility of IT therapy
total number of IT therapy cycles per participant
Impact of IT therapy on SOC management of CRS and ICANS
Number of inpatient hospital days among planned outpatient CAR T infusions. Number and type of systemic therapies for ICANS beyond steroids and IT therapy
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Vanderbilt-Ingram Cancer Center
Lead sponsor
Gilead Sciences
Collaborator
