This is a phase I/Ib imaging study of granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B (64Cu-GRIP B) Positron Emission Tomography (PET) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) receiving CD19-directed Chimeric antigen receptor T cells (CAR-T) therapy. The proposed study represents the first-ever lymphoma patient imaging studies with 64Cu-GRIP B PET. The tracer is designed to detect extracellular granzyme B as it is secreted by activated immune cells in the tumor microenvironment, which may highlight tumors that will exhibit a durable response to Cluster of Differentiation 19 (CD19)-directed CAR T-cell therapy.
Primary Objectives: 1\. To establish the feasibility of granzyme B detection with 64Cu-GRIP B PET in participants with relapsed/refractory NHL receiving CD19-directed CAR-T cell therapy in both cohorts. Secondary Objectives: 1. To descriptively report the patterns of intra-tumoral uptake of 64Cu-GRIP B on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-participant heterogeneity, and tumor-to-background signal in participants with participants with NHL. 2. To descriptively report the number of lesions identified on 64Cu-GRIP B PET compared with conventional imaging in participants with NHL. 3. To assess the safety of 64Cu-GRIP B in participants with NHL undergoing CAR-T cell therapy. Participants will be initially enrolled in Cohort 1. Based on the interim analysis, enrollment will begin in Cohort 2. An optional research biopsy will be collected after the post-therapy scan and participants will be followed for 12 months after the end of the study intervention.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
32
Given IV
Undergo imaging procedure
Undergo optional tumor biopsy
University of California, San Francisco
San Francisco, California, United States
RECRUITINGProportion of positive tumors at the post-CAR-T scan
The proportion of known lesions with detectable radiotracer uptake on conventional imaging will be reported along with 95% binomial exact confidence intervals. Tumors will be defined as positive if they are focally avid with maximum standardized uptake value (SUVmax) \>1.5 fold above adjacent background.
Time frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Mean SUVmax by disease site
The mean/sd (median and range, if normality assumption does not hold) for intra-tumoral SUVmax within lesions will be descriptively reported, to assess for intra-tumoral heterogeneity and differences in uptake by site of disease.
Time frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Overall Mean SUVmax by cohort
The mean/sd (median and range, if normality assumption does not hold) for inter-participant SUVmax within lesions will be descriptively reported, to assess for inter-participant heterogeneity and differences in uptake.
Time frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Percent of lymphoma lesions detected
The percentage of lesions detected on conventional imaging that are detected on baseline 64Cu-GRIP B PET will be descriptively reported.
Time frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Frequency and severity of treatment-emergent adverse events
Frequency and severity of treatment adverse events following 64Cu-GRIP B injection classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v 5.0).
Time frame: Up to 13 months
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