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

Status: Recruiting
Location: See location...
Intervention Type: Drug, Procedure
Study Type: Interventional
Study Phase: Phase 1
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: t
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• Disease characteristics, as defined by:

∙ Histologically-confirmed relapsed/refractory non-Hodgkin lymphoma 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%).

• Demonstrates adequate organ function as defined below:

∙ Absolute neutrophil count \>=1,500/microliter (mcL)

‣ Platelets ≥100,000/mcL

‣ Total bilirubin within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.

‣ Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \<=3 X institutional upper limit of normal.

‣ Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<=3 X institutional upper limit of normal

‣ Creatinine \<= 1.5 x within institutional upper limit of normal OR creatinine clearance Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2.

• Human immunodeficiency virus (HIV)-infected individuals on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

• Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. Individuals with HCV infection who are currently on treatment are eligible if an undetectable HCV viral load is demonstrated.

⁃ 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.

Locations
United States
California
University of California, San Francisco
RECRUITING
San Francisco
Contact Information
Primary
UCSF Hematopoietic Malignancies Clinical Trial Recruitment
HDFCCC.Heme@ucsf.edu
877-827-3222
Time Frame
Start Date: 2024-10-23
Estimated Completion Date: 2027-01-31
Participants
Target number of participants: 32
Treatments
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.
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.
Related Therapeutic Areas
Sponsors
Collaborators: The V Foundation
Leads: C. Babis Andreadis

This content was sourced from clinicaltrials.gov

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