Axicabtagene Ciloleucel Reinfusion for the Treatment of Relapsed and/or Refractory High-Risk Non-Hodgkin Lymphoma

Inclusion Criteria

• Histologically confirmed aggressive B cell non-Hodgkin lymphoma (NHL) including the following types defined by World Health Organization (WHO) 2008: * Diffuse large B cell lymphoma (DLBCL); OR * Primary mediastinal (thymic) large B cell lymphoma; OR * Transformation of follicular lymphoma, marginal zone lymphoma to DLBCL; OR * High grade B-cell lymphoma not otherwise specified (NOS) will also be included
• Subjects must be considered high-risk lymphoma (defined as lactate dehydrogenase [LDH] greater than upper limit of normal per institutional cut-off) at or within two weeks of leukapheresis
• At least 1 measurable lesion on PET-CT or CT scan. If the only measurable disease is lymph-node disease, at least 1 lymph node should be ≥ 1.5 cm
• Subjects must have received at least and a maximum one prior line of therapy for LBCL indication (i.e subjects receiving second line standard of care Axi-Cel will be enrolled in this study)
• Age 18 years or older
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1. ECOG 2 permitted if performance status is solely attributed to lymphoma
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
• Subjects of child‑bearing or child‑fathering potential must be willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the preparative lymphodepletion regimen
• Absolute neutrophil count (ANC) ≥ 1,000/uL
• Platelet count ≥ 75,000/uL
• Creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL/min
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (except in subjects with liver involvement by lymphoma)
• Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome
• Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as determined by an echocardiogram
• No clinically significant pleural effusion or ascites
• Baseline oxygen saturation > 92% on room air
• Ability to understand and the willingness to sign the written Institutional Review Board (IRB)‑approved informed consent document. Subjects unable to give informed consent will not be eligible for this study
• If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (flow cytometry or immunohistochemistry per the institutional criteria)
• Prior therapy washout of at least 2 weeks or 5 half- lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis
• REINFUSION ELIGIBILITY:
• Cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) should be either resolved or ≤ grade 1 at the time of Axi-Cel-2 infusion; and
• A second dose of Axi-Cel was generated to the targeted cell dose and meets all release criteria; and
• No active uncontrolled infection (antibiotics for febrile neutropenia permitted) at the time Axi-Cel-2 infusion, or any condition that in the opinion of the PI may pose an unacceptable risk to the subject

Exclusion Criteria

• Bridging therapy with steroids (e.g dexamethasone 40 mg for 5 days) and/or radiotherapy (at the discretion of the treating radiation oncologist) is permitted. No other forms of bridging therapy is permitted. If radiotherapy is used, at least 1 cm non- irradiated measurable lesion is required
• Prior treatment with CAR-T cell therapy
• Prior allogeneic transplant
• No active central nervous system disease from lymphoma. In patients with history of central nervous system (CNS) disease MRI of the brain and cerebrospinal fluid (CSF) analysis showing no evidence of CNS lymphoma
• Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of the reagents used in the Axi-Cel therapy
• History of Richter’s transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma
• Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment
• Women who are pregnant or breastfeeding
• History of invasive malignancy, unless the patient has been disease-free for five years * Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible * Hormonal therapy in subjects in remission > 1 year will be allowed
• History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication
• In the investigator’s judgment, the subject is unlikely to complete all study-specific visits or procedures, including follow-up visits, or comply with the study requirements for participation