Study of E7777 Prior to Kymriah for R/R DLBCL

Eligibility Criteria

• * Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah is planned, including:
• * diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
• * high grade B-cell lymphoma
• * DLBCL arising from follicular lymphoma
• * Considered at high risk for progression after CAR-T therapy by meeting one or more of the following factors:
• * refractory to last line of therapy
• * myc over expression \>40% in any prior biopsy
• * ≥2 sites of extranodal disease
• * Received two or more lines of systemic therapy
• * Has secured insurance coverage for Kymriah administration either in the outpatient or inpatient setting.
• * Age 18 years or older at the time of signing consent.
• * ECOG performance status of 0, 1, or 2
• * Adequate bone marrow reserve defined as:
• * Absolute neutrophil count (ANC) \> 1,000/mm\^3
• * Platelets ≥ 50,000/mm\^3 (transfusion support can be provided)
• * Hemoglobin \>8.0 mg/dl (transfusion support can be provided) Bone marrow involvement at disease assessment is an exclusion as these patients are at an increased risk of severe CRS and/or neurotoxicity
• * Adequate organ function at enrollment and within 14 days of planned E7777 treatment including:
• * renal function: eGFR ≥ 50 mL/min/1.73 m\^2
• * liver function: ALT ≤ 3 times the upper limit of normal (ULN) for age, AST ≤ 3 times the ULN, total bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN (if liver is involved by lymphoma, the exception are allowed upon approval of PI)
• * albumin ≥ 3.0 g/dl
• * Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea (CTCAE v5) and pulse oxygenation SpO2 \> 91% on room air. Pulmonary function tests within 28 days of enrollment: \>50% corrected DLCO and FEV1
• * Hemodynamically stable and LVEF ≥ 50% confirmed by echocardiogram or MUGA
• * Life expectancy ≥12 weeks in the opinion of the enrolling investigator as documented in the medical record
• * Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use birth control for at least 30 days after study treatment or at least at least 4 months after the final dose of CY, whichever is longer Female participants: Two forms of birth control, one of which must be a barrier method, for example: use of intrauterine device (IUD) or oral contraceptives, plus a barrier method such as a condom, diaphragm or cervical cap Male participants: If possible to father a child (unless a successful vasectomy with confirmed azoospermia) participant and female partner, must use adequate contraception
• * Written voluntary consent prior to the performance of any research related tests or procedures
• * Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
• * Known bone marrow involvement, if history of bone marrow involvement must have a BM biopsy to rule-out current involvement
• * Prior allogeneic transplant
• * Ocular disease or complaints visual acuity impairment, color or shape distortion, or blurred vision - potential participants are required to have an ophthalmological examine as part of screening
• * Known CNS involvement by malignancy - if clinically suspicious, must be ruled-out by examination of cerebrospinal fluid (CSF) by flow cytometry
• * Uncontrolled active hepatitis B or hepatitis C
• * Active or inactive HIV infection
• * Untreated active bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to enrollment)
• * History of heart failure or pulmonary edema, evidence of pleural effusion or active lower extremity edema
• * Uncontrolled unstable angina and/or myocardial infarction within 3 months of enrollment
• * Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion