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.

Study Overview

• Status: Terminated
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: [ 18F]F-AraG PET

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: [18F]F-AraG PET; 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; Dose: 5 mCi (±10%) Mode of Administration: Intravenous (IV); Other Names: [ 18F]F-AraG (2'-deoxy-2'-fluoro-9-β-D- arabinofuranosylguanine; trade name VisAcT)

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
First exploratory outcome measure	correlation between changes in SUV [18F]F-AraG signal on PET imaging to the observed clinical benefit rate using RECISTv1.1 criteria.	≥ 3 months
Second exploratory outcome measure	Correlation between changes in [18F]F-AraG signal to the frequency and grade of two common CAR T cell toxicities, cytokine release syndrome (CRS) and neurotoxicity, if observed in this study population.	≥ 3 months

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: CellSight Technologies, Inc.
• Investigators: Principal Investigator: David Miklos, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): May 9, 2022
• Study Completion (Actual): October 9, 2023

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: IRB-56655; CCT5038 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No