PET Imaging Study of 64Cu-GRIP B for Patients Receiving CD19-directed CAR-T Therapy

December 20, 2025 updated by: Michael Randall

A Phase I/Ib PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients Receiving CD19-directed CAR-T Therapy

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: UCSF Hematopoietic Malignancies Clinical Trial Recruitment
  • Phone Number: 877-827-3222
  • Email: HDFCCC.Heme@ucsf.edu

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael Randall, MD
        • Sub-Investigator:
          • Specer Behr, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Disease characteristics, as defined by:

    1. Histologically-confirmed relapsed/refractory non-Hodgkin lymphoma (NHL) with at least one prior line of therapy.
    2. Planned treatment with a commercially available CD19 targeting CAR-T cell product.
  2. Willing to undergo post-treatment tumor biopsies and has safely accessible soft tissue lesion.
  3. Age >= 18 years.
  4. Ability to understand and the willingness to sign a written informed consent document.
  5. Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >60%).
  6. Individuals with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  7. Individuals with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
  8. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. The effects of 64Cu-GRIP B on the developing human fetus are unknown. For this reason, participants of childbearing potential must agree to use adequate contraception: all participants should use barrier protection for the duration of study participation and for one month after last administration of study intervention. Should a participant become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Male participants treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and one month after last administration of study treatment.

Exclusion Criteria:

  1. Any condition that, in the opinion of the Principal Investigator, would impair the participant's ability to comply with study procedures.
  2. Pregnant participants are excluded from this study because the effects of 64Cu-GRIP B on the developing human fetus are unknown. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing parent with 64Cu-GRIP B, breastfeeding should be discontinued if the nursing parent receives 64Cu-GRIP B.
  3. Hypersensitivity to 64Cu-GRIP B or any of its excipients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: 64Cu-GRIP B PET imaging
Participants with NHL will undergo 64Cu-GRIP B PET before and after CD19-directed CAR-T therapy. Three participants will undergo post-treatment 64Cu-GRIP B PET at the Day 8 time point, three participants will undergo post-treatment 64Cu-GRIP B PET at the Day 15 (+/- 3) time point, and three participants will undergo post-treatment 64Cu-GRIP B PET Day 22 (+/- 3) time point. An optional soft tissue biopsy will be collected following the post-treatment PET. Participants will be followed up for 12 months after the final PET scan.
Drug: 64Cu-GRIP B
Given IV
Other Names:
  • granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B
Procedure: Positron Emission Tomography (PET)
Undergo imaging procedure
Other Names:
  • PET Scan
Procedure: Optional tumor biopsy
Undergo optional tumor biopsy
Other Names:
  • Biopsy
Experimental: Cohort 2: Expansion Phase 64Cu-GRIP B PET imaging
Participants with NHL will undergo 64Cu-GRIP B PET before and after CD19-directed CAR-T therapy with one of the three time points chosen based on 64Cu-GRIP B uptake determined in Cohort 1. An optional soft tissue biopsy will be collected following the post-treatment PET. Participants will be followed up for 12 months after the final PET scan.
Drug: 64Cu-GRIP B
Given IV
Other Names:
  • granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B
Procedure: Positron Emission Tomography (PET)
Undergo imaging procedure
Other Names:
  • PET Scan
Procedure: Optional tumor biopsy
Undergo optional tumor biopsy
Other Names:
  • Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of positive tumors at the post-CAR-T scan
Time Frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
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.
From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean SUVmax by disease site
Time Frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
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.
From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Overall Mean SUVmax by cohort
Time Frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
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.
From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Percent of lymphoma lesions detected
Time Frame: From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
The percentage of lesions detected on conventional imaging that are detected on baseline 64Cu-GRIP B PET will be descriptively reported.
From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total
Frequency and severity of treatment-emergent adverse events
Time Frame: Up to 13 months
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).
Up to 13 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michael Randall

Collaborators

The V Foundation

Investigators

  • Principal Investigator: Randall Michael, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2024

Primary Completion (Estimated)

January 31, 2027

Study Completion (Estimated)

January 31, 2027

Study Registration Dates

First Submitted

July 22, 2024

First Submitted That Met QC Criteria

July 22, 2024

First Posted (Actual)

July 26, 2024

Study Record Updates

Last Update Posted (Actual)

December 29, 2025

Last Update Submitted That Met QC Criteria

December 20, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24923
  • NCI-2024-05085 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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