PET Imaging for Non-Hodgkin's Lymphoma

Overseen By UCSF Hematopoietic Malignancies Clinical Trial Recruitment

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: C. Babis Andreadis

Must be taking: CD19 CAR-T therapy

Disqualifiers: Pregnancy, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new PET imaging technique for individuals with non-Hodgkin's lymphoma (a type of blood cancer) who have not responded to previous treatments and are about to receive CAR-T therapy. The study uses a special tracer, 64Cu-GRIP B (also known as 64Cu-labeled GRIP B or Copper-64 labeled Granzyme B), to determine if it can predict which tumors will respond well to the therapy. Participants will undergo PET scans before and after their CAR-T treatment to track changes. Those with relapsed or hard-to-treat non-Hodgkin's lymphoma who have previously tried other treatments might be a good fit. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What prior data suggests that this imaging method is safe for patients with non-Hodgkin's lymphoma?

Initial findings suggest that 64Cu-GRIP B, used in PET scans, offers a new method to detect active immune responses in tumors. This can help identify tumors that might respond well to CAR-T cell therapy. However, as this is an early-stage trial, information about its safety remains limited.

Previous studies have examined the safety of 64Cu-GRIP B in patients with various types of cancer. These studies aim to understand how the body processes the tracer and to ensure its safety for humans. So far, researchers have reported no major safety issues. However, it is important to note that they are still learning about how well people tolerate this treatment. Study participants will be closely monitored to ensure their safety throughout the process. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using 64Cu-GRIP B PET imaging for non-Hodgkin's lymphoma because it offers a unique way to visualize the disease's response to treatment. Unlike traditional imaging methods, this technique uses a special radioactive tracer, 64Cu-GRIP B, which can give more detailed and specific pictures of how effective CD19-directed CAR-T therapy is at different time points. This could lead to a better understanding of treatment efficacy and allow for more personalized treatment plans based on real-time imaging feedback. By potentially identifying changes in the lymphoma earlier than standard imaging, it might help in adjusting treatments more promptly for better patient outcomes.

What evidence suggests that 64Cu-GRIP B PET imaging is effective for detecting tumors in non-Hodgkin's lymphoma?

Research has shown that a special imaging technique called 64Cu-GRIP B PET can identify tumors in non-Hodgkin's lymphoma that might respond well to CD19-directed CAR-T cell therapy. In this trial, participants will undergo 64Cu-GRIP B PET imaging before and after receiving CD19-directed CAR-T therapy. This technique uses a tracer, 64Cu-GRIP B, to detect granzyme B, a protein released by immune cells when they attack cancer cells. By highlighting granzyme B, the imaging reveals which tumors are effectively targeted by the immune system. This could help predict a better response to CAR-T therapy, enabling doctors to create more personalized treatment plans. Although still in early stages, the study aims to make cancer treatments more precise by focusing on active immune responses. ^{1 4 6 7 8}

Who Is on the Research Team?

Randall Michael, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals with relapsed/refractory non-Hodgkin's lymphoma who are undergoing CD19-directed CAR-T therapy. Participants must meet certain health criteria to be eligible, but specific inclusion and exclusion details were not provided.

Inclusion Criteria

I agree to have biopsies after treatment and have a tumor that can be safely biopsied.

I can do most of my daily activities without help.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Any condition that would impair the participant's ability to comply with study procedures

Pregnant participants

I am allergic to 64Cu-GRIP B or its ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 64Cu-GRIP B PET imaging before and after CD19-directed CAR-T therapy

4 weeks

Multiple visits for PET imaging and CAR-T therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• 64Cu-GRIP B

Trial Overview

The study tests a new PET imaging agent called 64Cu-GRIP B in patients receiving CAR-T therapy. It aims to see if this tracer can identify which tumors will respond well to the treatment by detecting a molecule released by immune cells.

How Is the Trial Designed?

Group I: Cohort 2: Expansion Phase 64Cu-GRIP B PET imaging Experimental Treatment 3 Interventions

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 II: Cohort 1: 64Cu-GRIP B PET imaging Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

C. Babis Andreadis

Lead Sponsor

Trials

5

Recruited

130+

Michael Randall

Lead Sponsor

The V Foundation

Collaborator

Trials

10

Recruited

320+

Published Research Related to This Trial

The study developed novel SPECT imaging probes, [111 In]IDT and [111 In]IDAT, which effectively target granzyme B, a promising biomarker for enhancing immune checkpoint inhibitor treatments.

In experiments with tumor-bearing mice, these probes demonstrated moderate accumulation in tumors, correlating with granzyme B expression, suggesting their potential utility in monitoring treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of 111 In-labeled tetrapeptide-based compounds as single-photon emission computed tomography imaging probes targeting granzyme B. Kazuta, N., Watanabe, H., Ono, M.[2023]

Granzyme B PET imaging using the targeted peptide GZP is a highly sensitive and specific method for early assessment of response to cancer immunotherapy, showing 93% sensitivity and 94% negative predictive value in predicting treatment outcomes.

The study demonstrated that GZP PET imaging can effectively compare the efficacy of different checkpoint inhibitor regimens, revealing that sequential dosing of PD-1 and CTLA-4 therapies is as effective as concurrent administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging. Larimer, BM., Bloch, E., Nesti, S., et al.[2020]

The chelator pycup and its derivatives provide strong stability for (64)Cu in PET imaging, showing very slow decomplexation even under harsh conditions, which is crucial for effective imaging.

In vivo studies demonstrated that pycup2A, when conjugated to a fibrin-targeted peptide, successfully enabled PET imaging of arterial thrombosis in a rat model, highlighting its potential for targeted diagnostic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pycup--a bifunctional, cage-like ligand for (64)Cu radiolabeling. Boros, E., Rybak-Akimova, E., Holland, JP., et al.[2021]

The study developed a method to reduce kidney radioactivity from Copper-64 (64Cu)-labeled antibody fragments by designing a compound that liberates a radiometabolite for urinary excretion, which is beneficial for molecular imaging and radioimmunotherapy.

When tested in mice, the new 64Cu-labeled antibody fragment showed similar tumor targeting but significantly lower kidney radioactivity compared to traditional methods, indicating improved safety without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copper-64-Labeled Antibody Fragments for Immuno-PET/Radioimmunotherapy with Low Renal Radioactivity Levels and Amplified Tumor-Kidney Ratios. Suzuki, H., Kise, S., Kaizuka, Y., et al.[2021]

A new imaging technology, using a specially engineered peptide called GRIP B, allows researchers to measure the activity of granzyme B (GZMB) in living organisms, providing insights into its biological functions in real-time.

In mouse cancer models, this method successfully detected GZMB activity in tumors and lymphoid tissues, indicating its potential role in immune responses, especially when combined with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET. Zhao, N., Bardine, C., Lourenço, AL., et al.[2023]

The study demonstrated that the PET imaging agent [18F]AlF-mNOTA-GZP can effectively differentiate between cancer treatment responders and non-responders in a mouse model, indicating its potential as a biomarker for assessing the effectiveness of combined chemotherapy and immune checkpoint inhibitor therapies.

The uptake of [18F]AlF-mNOTA-GZP was positively correlated with the presence of Granzyme B-expressing immune cells, such as GZB+ CD8+ T cells and GZB+ NK+ cells, suggesting that Granzyme B plays a crucial role in the immune response to treatment and can serve as a reliable indicator of tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granzyme B PET Imaging of Combined Chemotherapy and Immune Checkpoint Inhibitor Therapy in Colon Cancer. Goggi, JL., Hartimath, SV., Xuan, TY., et al.[2022]

In a study of 69 lymphoma cases in the upper aerodigestive tract, granzyme B was found to be a reliable marker for diagnosing T/NK-cell lymphomas, as all cases expressing CD56 and T-cell markers showed strong granzyme B immunoreactivity.

The monoclonal antibody to granzyme B (GrB-7) proved effective for diagnosis without needing special tissue processing techniques, making it a practical tool for identifying T/NK-cell lymphomas alongside CD56.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granzyme B immunoreactivity in T/natural killer cell lymphomas. Cho, MS., Lee, MK., Yang, WI., et al.[2015]

A novel granzyme B-targeted PET imaging agent (GZP) was successfully used in a murine model to non-invasively identify immune-related adverse events (irAEs) associated with cancer immunotherapy, highlighting its potential for monitoring these events in patients.

The study found that GZP PET imaging showed increased uptake in organs affected by irAEs, such as the colon and spleen, which decreased after treatment with the immunosuppressor dexamethasone, indicating a direct correlation between granzyme B presence and the severity of irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive Detection of Immunotherapy-Induced Adverse Events. Ferreira, CA., Heidari, P., Ataeinia, B., et al.[2022]

The study demonstrated that 64Cu-labeled ch14.18 antibodies can specifically target neuroblastoma tumors, achieving a high accumulation rate of 31.6% ID/g in preclinical models, indicating their potential efficacy for targeted therapy.

Clinical PET/MRI scans using the radiolabeled antibodies successfully visualized neuroblastoma metastases in a patient, suggesting that this theranostic approach could be a valuable tool for therapy planning in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational immunoPET imaging using a radiolabeled GD2-specific antibody in neuroblastoma. Schmitt, J., Schwenck, J., Maurer, A., et al.[2022]

Researchers developed new near-infrared fluorogenic substrates that can detect active granzyme A (GzmA) in both human and mouse models, providing a highly efficient and selective tool for studying immune responses against tumors.

These probes allow for real-time imaging of how cytotoxic immune cells, like T lymphocytes and natural killer cells, respond to cancer cells, enhancing our understanding of the immune response in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity. Cheng, Z., Thompson, EJ., Mendive-Tapia, L., et al.[2023]

The phase 1 trial demonstrated that 64Cu-daratumumab PET/CT is a safe imaging technique for detecting multiple myeloma, with no significant adverse events reported in 12 patients.

Using 45 mg of unlabeled daratumumab improved image quality by reducing background signal, suggesting that 64Cu-daratumumab may offer better sensitivity and specificity compared to traditional FDG PET/CT for identifying multiple myeloma lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab. Krishnan, A., Adhikarla, V., Poku, EK., et al.[2022]

The VLA4-targeted radiopharmaceutical 64Cu-LLP2A demonstrated a favorable safety profile in both animal and human studies, with no adverse effects observed in human participants after administration.

In human trials, 64Cu-LLP2A showed effective biodistribution and rapid clearance from the bloodstream, making it a promising imaging agent for multiple myeloma, with optimal imaging occurring 4-5 hours post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Humans Evaluation of Safety and Dosimetry of 64Cu-LLP2A for PET Imaging. Laforest, R., Ghai, A., Fraum, TJ., et al.[2023]

The PET imaging technique using the granzyme B-targeted radiotracer 68Ga-grazytracer can effectively predict tumor responses to immunotherapy, showing better sensitivity in distinguishing responders from nonresponders compared to traditional methods.

In a preliminary clinical trial with 5 patients, 68Ga-grazytracer was safe with no adverse events reported, and its PET results correlated well with clinical responses to immunotherapy, suggesting its potential for improving patient stratification and early response assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy. Zhou, H., Wang, Y., Xu, H., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT06522932

PET Imaging Study of 64Cu-GRIP B for Patients Receiving ...

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) ...

2.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT06522932

PET Imaging Study of 64Cu-GRIP B for Patients Receiving ...

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.

3.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04001

Radiotracer (64Cu-GRIP B) Targeting Granzyme B with ...

This phase I/II clinical trial evaluates if using a radiotracer called 64 Cu-GRIP B with positron emission tomography (PET) imaging can be safe and useful for ...

4.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/trial/listing/408735

64Cu-GRIP B in Patients With Advanced Malignancies

Granzyme B (GrB) is a biomarker produced by immune cells in response to immunotherapy, which may highlight tumors that are more likely to respond to treatment.

5.

urotoday.com

urotoday.com/clinical-trials/prostate-cancer/154998-a-first-in-human-phase-i-ii-pet-imaging-study-of-64cu-grip-b-a-radiotracer-targeting-granzyme-b-in-patients-with-advanced-genitourinary-malignancies.html?tags=14636

A First-in-Human, Phase I/II PET Imaging Study of 64Cu ...

A First-in-Human, Phase I/II PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients With Advanced Malignancies ...

6.

careacross.com

careacross.com/clinical-trials/trial/NCT06522932

PET Imaging Study of 64Cu-GRIP B for Patients Receiving ...

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 ...

7.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT05888532

64Cu-GRIP B in Patients With Advanced Malignancies

PRIMARY OBJECTIVES: To determine the safety, dosimetry, and pharmacokinetics of 64Cu-GRIP B PET in patients with solid tumor malignancy (3 males ...

8.

clinicaltrials.ucbraid.org

clinicaltrials.ucbraid.org/non-hodgkin-lymphoma

University of California Health Non-Hodgkin Lymphoma ...

This is a phase I/Ib imaging study of granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B (64Cu- ...