E7777 to Enhance Regulatory T-Cell Depletion Prior to CAR-T for the Treatment of Relapsed/Refractory B-Cell Lymphomas

Inclusion Criteria

• Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah, Yescarta or Breyanzi is planned, including: * Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, * High grade B-cell lymphoma * DLBCL arising from follicular lymphoma * Primary mediastinal lymphoma * Follicular lymphoma grade 3B
• 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 * Elevated lactate dehydrogenase (LDH) (above upper limit of normal [ULN]) at the time of relapse
• Has secured insurance coverage for Kymriah, Yecarta or Breyanzi administration either in the outpatient or inpatient setting
• Age 18 years or older at the time of signing consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• 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)
• Estimated glomerular filtration rate (eGFR) >= 50 mL/min/1.73 m^2 (within 14 days of planned E7777 treatment)
• Alanine aminotransferase (ALT) =< 3 times the upper limit of normal (ULN) for age (within 14 days of planned E7777 treatment)
• Aspartate aminotransferase (AST) =< 3 times the ULN (within 14 days of planned E7777 treatment)
• 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 principal investigator [PI]) (within 14 days of planned E7777 treatment)
• Albumin >= 3.0 g/dl (within 14 days of planned E7777 treatment)
• Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) and pulse oxygenation SpO2 > 91% on room air
• Pulmonary function tests within 28 days of enrollment: > 50% corrected carbon monoxide diffusing capability (DLCO) and forced expiratory volume in 1 second (FEV1)
• Hemodynamically stable and left ventricular ejection fraction (LVEF) >= 50% confirmed by echocardiogram or multigated acquisition scan (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 cyclophosphamide (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

Exclusion Criteria

• 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)
• Prior allogeneic transplant
• Active acute 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. Chronic stable conditions are not an exclusion
• Active central nervous system (CNS) involvement by malignancy - prior history must be confirmed by negative examination of cerebrospinal fluid (CSF) by flow cytometry or brain magnetic resonance imaging (MRI).
• Uncontrolled active hepatitis B or hepatitis C
• Active or inactive human immunodeficiency virus (HIV) infection
• Untreated active bacterial, viral or fungal infection (e.g. blood culture positive =< 72 hours prior to enrollment
• Uncontrolled heart failure defined as New York Heart Association class 2 or greater, > grade 1 lower extremity edema associated with heart failure, pulmonary edema, or current evidence of significant pleural effusion as determined by the clinical investigator
• 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
• Receipt of chemotherapy or immunotherapy [defined as immune checkpoint inhibitors, monoclonal antibodies] within 7 days prior to E7777 infusion.