Evaluate Safety of Axicabtagene Ciloleucel Reinfusion (Axi-Cel-2) in Patients With Relapsed and/or Refractory Second Line High-Risk Non-Hodgkin Lymphoma After Standard of Care Axi-Cel

Eligibility Criteria

• 1. Diagnosis: Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008:
• * Diffuse large B cell lymphoma (DLBCL); OR
• * primary mediastinal (thymic) large B cell lymphoma; OR
• * transformation of follicular lymphoma (TFL), marginal zone lymphoma to DLBCL; OR
• * high grade B-cell Lymphoma NOS will also be included
• 2. Patients must be considered high-risk lymphoma (defined as LDH greater than upper limit of normal per institutional cut-off) at or within two weeks of leukapheresis.
• 3. 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).
• 4. 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.
• 5. Age 18 years or older
• 6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1. ECOG 2 permitted if performance status is solely attributed to lymphoma.
• 7. Normal Organ and Marrow Function
• * ANC ≥ 1,000/uL
• * Platelet count ≥ 75,000/uL
• * Adequate renal, hepatic, pulmonary and cardiac function defined as:
• * Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
• * Serum ALT or AST ≤ 2.5 x 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
• 8. Ability to understand and the willingness to sign the written IRB-approved informed consent document. Subjects unable to give informed consent will not be eligible for this study.
• 9. 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)
• 10. Contraception: 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 twelve (12) months after receiving the preparative lymphodepletion regimen.
• 11. If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (Flow cytometry or immunohistochemistry per the institutional criteria)
• 12. 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
• 1. Prior treatment with CAR-T or adoptive cell therapy.
• 2. Prior allogeneic transplant.
• 3. No bridging therapy permitted except for steroids or radiotherapy (bridging therapy with steroids e.g. dexamethasone 40 mg for 5 days or radiotherapy is permitted). Measurable non-irradiated lesion post-apheresis needed for enrollment.
• 4. Active central nervous system disease from lymphoma. MRI of the brain with no evidence of CNS lymphoma if prior history of CNS involvement.
• 5. Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of the reagents used in the Axi-Cel infusion.
• 6. History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
• 7. Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment.
• 8. Women who are pregnant or breastfeeding
• 9. 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, and breast) is eligible.
• * Hormonal therapy in subjects in remission \>1 year will be allowed.
• 10. History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication.
• 11. 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.