NCT06522932

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
9mo left

Started Oct 2024

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress68%
Oct 2024Jan 2027

First Submitted

Initial submission to the registry

July 22, 2024

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 26, 2024

Completed
3 months until next milestone

Study Start

First participant enrolled

October 23, 2024

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2027

Last Updated

December 29, 2025

Status Verified

December 1, 2025

Enrollment Period

2.3 years

First QC Date

July 22, 2024

Last Update Submit

December 20, 2025

Conditions

Keywords

CAR-T therapyImaging

Outcome Measures

Primary Outcomes (1)

  • Proportion 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.

    From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total

Secondary Outcomes (4)

  • Mean SUVmax by disease site

    From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total

  • Overall Mean SUVmax by cohort

    From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total

  • Percent of lymphoma lesions detected

    From prior to CAR-T to Day 22 following CAR-T cell, approximately 32 days total

  • Frequency and severity of treatment-emergent adverse events

    Up to 13 months

Study Arms (2)

Cohort 1: 64Cu-GRIP B PET imaging

EXPERIMENTAL

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 BProcedure: Positron Emission Tomography (PET)Procedure: Optional tumor biopsy

Cohort 2: Expansion Phase 64Cu-GRIP B PET imaging

EXPERIMENTAL

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 BProcedure: Positron Emission Tomography (PET)Procedure: Optional tumor biopsy

Interventions

Given IV

Also known as: granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B
Cohort 1: 64Cu-GRIP B PET imagingCohort 2: Expansion Phase 64Cu-GRIP B PET imaging

Undergo imaging procedure

Also known as: PET Scan
Cohort 1: 64Cu-GRIP B PET imagingCohort 2: Expansion Phase 64Cu-GRIP B PET imaging

Undergo optional tumor biopsy

Also known as: Biopsy
Cohort 1: 64Cu-GRIP B PET imagingCohort 2: Expansion Phase 64Cu-GRIP B PET imaging

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Disease characteristics, as defined by:
  • Histologically-confirmed relapsed/refractory non-Hodgkin lymphoma (NHL) with at least one prior line of therapy.
  • Planned treatment with a commercially available CD19 targeting CAR-T cell product.
  • Willing to undergo post-treatment tumor biopsies and has safely accessible soft tissue lesion.
  • Age \>= 18 years.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%).
  • Individuals with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • 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.
  • 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.

You may not qualify if:

  • Any condition that, in the opinion of the Principal Investigator, would impair the participant's ability to comply with study procedures.
  • 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.
  • Hypersensitivity to 64Cu-GRIP B or any of its excipients.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

GranzymesMagnetic Resonance SpectroscopyBiopsy

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesCytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, Operative

Study Officials

  • Randall Michael, MD

    University of California, San Francisco

    PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Hematopoietic Malignancies Clinical Trial Recruitment

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 22, 2024

First Posted

July 26, 2024

Study Start

October 23, 2024

Primary Completion (Estimated)

January 31, 2027

Study Completion (Estimated)

January 31, 2027

Last Updated

December 29, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations