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

Phase 2

Recruiting

• Conditions: Non-Hodgkin's Lymphoma
• Interventions: Drug: [ 18F]F-AraG PET

• Registration Number: NCT05096234
• Lead Sponsor: Stanford University

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2021-09-28
• Study First Submitted: 2021-10-14
• Study First Submitted QC: 2021-10-14
• Study First Posted: 2021-10-27
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-15
• Last Update Posted: 2023-05-17
• Primary Completion: 2024-06
• Study Completion: 2024-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[18F]F-AraG PET	[ 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

Primary Outcome Measures

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

Trial Locations

Locations (1)

Stanford University, School of Medicine; 🇺🇸 Stanford, California, United States