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

NCT ID: NCT06522932

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-23

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non Hodgkin Lymphoma

Keywords

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CAR-T therapy Imaging

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

64Cu-GRIP B

Intervention Type DRUG

Given IV

Positron Emission Tomography (PET)

Intervention Type PROCEDURE

Undergo imaging procedure

Optional tumor biopsy

Intervention Type PROCEDURE

Undergo optional tumor biopsy

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.

Group Type EXPERIMENTAL

64Cu-GRIP B

Intervention Type DRUG

Given IV

Positron Emission Tomography (PET)

Intervention Type PROCEDURE

Undergo imaging procedure

Optional tumor biopsy

Intervention Type PROCEDURE

Undergo optional tumor biopsy

Interventions

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64Cu-GRIP B

Given IV

Intervention Type DRUG

Positron Emission Tomography (PET)

Undergo imaging procedure

Intervention Type PROCEDURE

Optional tumor biopsy

Undergo optional tumor biopsy

Intervention Type PROCEDURE

Other Intervention Names

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granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B PET Scan Biopsy

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The V Foundation

OTHER

Sponsor Role collaborator

Michael Randall

OTHER

Sponsor Role lead

Responsible Party

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Michael Randall

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Randall Michael, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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UCSF Hematopoietic Malignancies Clinical Trial Recruitment

Role: CONTACT

Phone: 877-827-3222

Email: [email protected]

Facility Contacts

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UCSF Hematopoietic Malignancies Clinical Trial Recruitment

Role: primary

Role: backup

Other Identifiers

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NCI-2024-05085

Identifier Type: REGISTRY

Identifier Source: secondary_id

24923

Identifier Type: -

Identifier Source: org_study_id