A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma

Inclusion Criteria:

Eligible subjects will be considered for inclusion if they meet all of the following criteria:

• Men and women 18 years of age or older

• Histologically proven FL (Grade 1-3A) on most recent biopsy, history of transformedfollicular lymphoma permitted at clinician discretion)

• Patients with follicular lymphoma must have disease that has relapsed or isrefractory to 2 or more prior lines of systemic therapy

• (ECOG) performance status of 0-2

• Medically appropriate for CAR-T cell therapy: adequate organ function CrCL >/= 45mL/min/m2, hemoglobin level ≥ 8 g/dl, serum alanine aminotransferase (ALT)/aspartateaminotransferase (AST) levels ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN ifdocumented liver involvement, baseline oxygen saturation levels (SpO2) ≥92% on roomair

• Have at least 1 measurable lesion on imaging, defined as a lesion that can beaccurately measured in at least one dimension (longest diameter to be recorded fornon-nodal lesions and short axis for nodal lesions) and ≥1 cm on CT, MRI, orclinical exam.

• Prior radiation therapy is permitted provided normal tissue tolerance is notexceeded

• Female of child-bearing potential (FOCBP, defined below) must have a negativepregnancy test within 1 week of simulation for RT

• Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

• History of other (non B-cell lymphoma) invasive malignancy requiring active therapy (systemic therapy, radiation, or surgery) within the past 3 years, excludingnon-melanomatous skin cancer

• Women of childbearing potential who are pregnant

• Women who are breastfeeding and unwilling to discontinue prior to lymphodepletingchemotherapy and for 12 months following lymphodepleting chemotherapy and CAR-T cellinfusion

• Urgent need for bridging chemotherapy or rituximab between apheresis and CAR T cellproduct infusion (steroids permitted)

• Additional RT would exceed standard organ at risk constraints

• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides

• Uncontrolled fungal, bacterial, or viral infection requiring intravenousantimicrobials for management. Urinary tract infection and uncomplicated bacterialpharyngitis is permitted if responding to active treatment. Recent COVID19 infectionis permitted if patient is deemed medically stable for CAR-T cell therapy.