18F-F-AraG PET Imaging to Evaluate Immunological Response to CAR T Cell Therapy in Lymphoma

Study Overview
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Brief Summary
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This is a pilot study in adult subjects with aggressive B-cell lymphoma who will receive commercial or research CAR T cell therapy as anticancer treatment.

Detailed Description
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Primary Objectives: * Explore the relationship of change in [18F]F-AraG PET signal following CAR T cell treatment with changes in T cell infiltration in tumor biopsies. Exploratory Analyses: Explore the relationship of change in [18F]F-AraG PET signal in tumor lesions following CAR T cell treatment with clinical benefit rate (defined as Complete Response (CR) + Partial Response (PR) + stable disease (SD) ≥ 3 months) using RECISTv1.1 criteria Correlate the change in [18F]F-AraG PET signal in tumor lesions following CAR T cell therapy with maximum grade of Cytokine Release Syndrome (CRS) and neurotoxicity experienced.

Official Title
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Pilot Study of [18F]F-AraG PET Imaging to Evaluate Immunological Response to Chimeric Antigen Receptor (CAR) T Cell Therapy in Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: [ 18F]F-AraG PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008: DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR primary mediastinal (thymic) large B cell lymphoma transformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia to DLBCL will also be included Measurable disease by PET imaging (as defined by Cheson (2014)), that meets all the following criteria: At least one measureable lesion away from head & neck, liver, kidneys, GI tract and bladder At least one biopsy-accessible lesion or lymph node. Express willingness to undergo low risk FNA or core biopsy of subcutaneous accessible lesion or lymph node. Scheduled to receive commercial or research CAR T cell therapy with axicabtagene ciloleucel (Yescarta ®) as part of anticancer therapy. Adequate renal and hepatic function, defined as: Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min or Cr < 1.6 mg/dL Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5x upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dL, except in cases of Gilbert's syndrome Able to give informed consent. Subjects unable to give informed consent will not be eligible for this study Exclusion Criteria: Women who are pregnant or breastfeeding. Subjects with significant GI disease involvement by PET imaging In the investigator's judgment, have any medical condition likely to interfere with assessment of safety or efficacy, be unable to tolerate additional radiation, or be unlikely to complete all protocol-required visits and procedures.

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [18F]F-AraG PET<br>Subjects will undergo PET imaging at the following time points: Baseline, prior to lymphodepleting chemotherapy: [18F]F-AraGPET/CT, followed the next day by FDG-PET/CT At peak CAR expansion: Day 4 (± 2 days) post-CAR infusion: [18F]F-AraG PET At Day +28 (± 4 days) post-CAR infusion: FDG-PET/CT Subjects will have a paired biopsy after each imaging time point, if possible. Subjects will be followed for safety of [18F]F-AraG for 30 days after last dose | Drug: [ 18F]F-AraG PET<br>* Dose: 5 mCi (±10%) Mode of Administration: Intravenous (IV)<br>* Other names: [ 18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D- arabinofuranosylguanine; trade name VisAcT);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary outcome measure | Spearman correlation between changes in SUV in [18F]F-AraG signal on PET imaging to changes in T-cell infiltrates in biopsy samples | values obtained on Day 0 and Day 4 (± 2 days) |