18F-F-AraG PET Imaging to Evaluate Immunological Response to CAR T Cell Therapy in Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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
Other Outcome Measures
- First exploratory outcome measure [≥ 3 months]
correlation between changes in SUV [18F]F-AraG signal on PET imaging to the observed clinical benefit rate using RECISTv1.1 criteria.
- Second exploratory outcome measure [≥ 3 months]
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.
Eligibility Criteria
Criteria
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
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Measurable disease by PET imaging (as defined by Cheson (2014)), that meets all the following criteria:
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At least one measureable lesion away from head & neck, liver, kidneys, GI tract and bladder
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At least one biopsy-accessible lesion or lymph node.
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Express willingness to undergo low risk FNA or core biopsy of subcutaneous accessible lesion or lymph node.
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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
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University, School of Medicine | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
- CellSight Technologies, Inc.
Investigators
- Principal Investigator: David Miklos, MD, PhD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-56655
- CCT5038