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

Study Overview
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Brief Summary
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To learn about the safety of a drug called axicabtagene ciloleucel given in combination with radiation therapy to patients with relapsed/refractory FL.

Detailed Description
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Primary Objectives: -The primary objective of this study is to determine the safety of standard of care axicabtagene ciloleucel with bridging radiotherapy (RT) in patients with relapsed/refractory follicular lymphoma, as assessed by the incidence of grade 3 or higher cytokine release syndrome (CRS) within 30 days after chimeric antigen receptor (CAR) T-cell infusion. Secondary Objectives: Establish the rates of CRS and ICANS in patients treated with CAR T-cell therapy and radiation Determine complete response rate (CR) at approximately 1 month post CAR T-cell ---therapy Determine the overall response rate (ORR) Determine the duration of response (DOR) Determine progression free survival (PFS) Determine overall survival (OS) Exploratory Objectives: -Assess the impact of tumor burden as measured by metabolic tumor volume and total lesion glycolysis on PET/CT on response following CAR T-cell infusion

Official Title
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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

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Axicabtagene Ciloleucel
* Drug: Cyclophosphamide
* Drug: Fludarabine phosphate
* Drug: Prednisone
* Drug: Diphenhydramine
* Drug: Acetaminophen


Participation Criteria
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Eligibility Criteria
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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) Relapsed or refractory following 2 or more prior lines of systemic therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Medically appropriate for CAR-T cell therapy: adequate organ function CrCL >/= 45 mL/min/m2, hemoglobin level ≥ 8 g/dl, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement, baseline oxygen saturation levels (SpO2) ≥92% on room air Have at least 2 measurable lesions on imaging, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) and ≥1 cm on CT, MRI, or clinical exam. At least one lesion will be omitted from the radiation treatment field. Prior radiation therapy is permitted provided normal tissue tolerance is not exceeded Female of child-bearing potential (FOCBP, defined below) must have a negative pregnancy test within 1 week of simulation for RT Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Histologic evidence of transformed follicular lymphoma, or follicular lymphoma grade 3B History of invasive malignancy requiring active therapy (systemic therapy, radiation, or surgery) within the past 3 years, excluding non-melanomatous skin cancer Women of childbearing potential who are pregnant Women who are breastfeeding and unwilling to discontinue prior to lymphodepleting chemotherapy and for 12 months following lymphodepleting chemotherapy and CAR-T cell infusion Urgent need for bridging chemotherapy or rituximab between apheresis and CAR T cell product 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 intravenous antimicrobials for management. Urinary tract infection and uncomplicated bacterial pharyngitis is permitted if responding to active treatment. Recent COVID19 infection is permitted if patient is deemed medically stable for CAR-T cell therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axicabtagene Ciloleuce<br>Participants will first have a procedure to collect your white blood cells that will be used to make axicabtagene ciloleucel. Then participatns will receive radiation therapy, followed by conditioning chemotherapy and 1 infusion of axicabtagene ciloleucel. | Drug: Axicabtagene Ciloleucel<br>* Given by IV (vein)<br>Drug: Cyclophosphamide<br>* Given by IV (vein)<br>* Other names: Neosar®;Drug: Fludarabine phosphate<br>* Given by IV (vein)<br>Drug: Prednisone<br>* Given by IV (vein)<br>Drug: Diphenhydramine<br>* Given by IV (vein)<br>* Other names: Benadryl®;Drug: Acetaminophen<br>* Given by IV (vein)<br>* Other names: Ofirmev™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |  | through study completion; an average of 1 year |