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

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

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.

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.

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:

  1. Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min or Cr < 1.6 mg/dL
  2. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5x upper limit of normal (ULN)
  3. 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.