Lazarus: IT Therapy for ICANS

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. Researchers will compare Axi-cel to Brexu-cel see if there will be a reduction in ICANS when compared to historical experience.

Inclusion Criteria: 1. Age ≥ 18 years 2. Histologically confirmed non-Hodgkin Lymphoma, including the following types defined by the World Health Organization (2017) or International Consensus Classification (2022): * Diffuse large B-cell lymphoma (DLBCL) * Primary mediastinal large B-cell lymphoma (PMBCL) * Transformed follicular lymphoma (tFL) * Transformed marginal zone lymphoma (tMZL) * High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements * Follicular lymphoma * Mantle cell lymphoma * Marginal zone lymphoma 3. Meets institutional eligibility criteria to receive standard of care CD19 CAR T therapy. 4. The participant (or legally acceptable representative if applicable) has provided documented informed consent for the trial. 5. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to allocation. Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests, including HBsAg and anti-HBc, are required for all participants. 6. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. * Participants must have completed curative anti-viral therapy at least 4 weeks prior to allocation. * Hepatitis C screening tests are not required unless: Known history of HCV infection as mandated by local health authority or institutional requirement for CAR T 7. Participants with HIV are eligible if they meet ALL of the following criteria: * The CD4 count is ≥ 350 cells/µL at screening * The HIV viral load is below the detectable level as per locally available testing * Are on a stable ART regimen for at least 4 weeks prior to study entry with good compliance * Note: ART includes drugs, which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study). * HIV screening tests are not required unless: Known history of HIV infection as mandated by local health authority or institutional requirement for CAR T 8. Adequate organ function as defined in the following table. Specimens must be collected within 30 days of LD chemo. Absolute neutrophil count (ANC) ≥500/µL a Platelets ≥25 000/µL a Hemoglobin ≥7 g/dL a Renal Creatinine OR Measured or calculated b creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN (except known case of Gilbert's) AST (SGOT) and ALT (SGPT) ≤ 5× ULN Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 9. Participants Assigned Male Sex at Birth If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is: * Cytarabine: 1 month * Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR * Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below: * Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak. Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate. Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed. 10. Participants Assigned Female Sex at Birth A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a person of childbearing potential (POCBP) OR Is a POCBP and: Uses a contraceptive method that is highly effective (with a failure rate of \6 months prior to full study screening and considered to have a very low risk of recurrence; or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. * Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence * Other malignancy that is considered cured with minimal risk of recurrence. * Known indolent bone marrow disorders such as monoclonal gammopathy of undetermined significance, clonal hematopoiesis of indeterminate potential that in the opinion of the Investigator or Sponsor do not present an increased risk of developing a secondary hematopoietic malignancy. 7. A POCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for participant to start receiving study medication. 8. Primary CNS lymphoma, post-transplant lymphoproliferative disorder (PTLD) 9. Any history of active CNS involvement with lymphoma. Previously treated secondary CNS disease allowed as long as confirmed disease control based on imaging and negative CSF cytology. 10. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. 11. Is currently enrolled on another interventional therapeutic clinical trial which may impact the safety and/or efficacy of CAR T therapy. 12. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication. 13. Has active autoimmune disease on active therapy with systemic biologics and/or prednisone ≥ 20mg/day equivalent. Vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are allowed to enroll. 14. Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications. Note: Tumor biopsy and placement of central venous access devices are not considered major surgery. 15. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator. 16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.