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

Stanford University

Status and phase: Terminated; Phase 1

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: [ 18F]F-AraG PET

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05096234

IRB-56655

CCT5038 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

[18F]F-AraG PET

Experimental group

Description:

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

Treatment:

Drug: [ 18F]F-AraG PET