RecruitingInterventionalPhase 1

Pilot PET Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma

NCT ID: NCT05892393Sponsor: Robert Flavell, MD, PhDLast updated: 2026-06-15

Summary

This phase I trial tests the safety of \[89Zr\]DFO-YS5 positron emission tomography (PET) imaging and how well it works to detect CD46 positive cancer cells in patients with multiple myeloma. \[89Zr\]DFO-YS5 is an imaging agent called a radiopharmaceutical tracer. A radiopharmaceutical tracer uses a small amount of radioactive material that is injected into a vein to help image different areas of the body. \[89Zr\]DFO-YS5 targets a specialized protein called CD46, which is in certain multiple myeloma cancer cells, and \[89Zr\]DFO-YS5 PET scans may improve detection of multiple myeloma.

Detailed description

PRIMARY OBJECTIVE: I. To determine the sensitivity of metastatic lesion detection in multiple myeloma using zirconium Zr 89-DFO-YS5 (\[89Zr\]DFO-YS5 PET, as compared with fludeoxyglucose F-18 (18F-FDG) PET imaging. SECONDARY OBJECTIVES: I. To determine the safety of \[89Zr\]DFO-YS5. II. To determine the average organ uptake of \[89Zr\]DFO-YS5. III. To descriptively report the patterns of intra-tumoral uptake of \[89Zr\]DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal. IV. To calculate the dosimetry of \[89Zr\]DFO-YS5 in patients with multiple myeloma. EXPLORATORY OBJECTIVE: I. To determine the association between uptake (standardized uptake value maximum \[SUVmax\]) of \[89Zr\]DFO-YS5 with 1q amplification by fluorescence in situ hybridization (FISH) on tumor biopsies (when available; FISH may be conducted as part of routine, standard-of-care). OUTLINE: Participants are assigned to 1 of 2 cohorts based on participant preference. COHORT A: Participants receive \[89Zr\]DFO-YS5 intravenously (IV) and undergo a single PET/CT or PET/MRI scan 5-7 days post-injection. Participants also receive fludeoxyglucose F-18 IV and undergo PET/CT or PET/MRI scan within 28 days prior to day 1. COHORT B: Participants receive \[89Zr\]DFO-YS5 IV and undergo four PET/CT or PET/MRI scans on days 1, 2, 3-4, and 5-7 post-injection. Participants also receive fludeoxyglucose F-18 IV and undergo PET/CT or PET/MRI scan within 28 days prior to day 1. Patients are followed up at 30 days after final scan.

Arms & interventions

DrugZirconium Zr 89-DFO-YS5
Given IV
ProcedurePositron Emission Tomography / Computed Tomography (PET/CT)
Positron emission tomography-computed tomography is a nuclear medicine technique which combines, in a single gantry, a positron emission tomography scanner and an x-ray computed tomography scanner, to acquire sequential images from both devices in the same session, which are combined into a single superposed image
ProcedurePositron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)
Positron emission tomography-magnetic resonance imaging is a hybrid imaging technology that incorporates magnetic resonance imaging soft tissue morphological imaging and positron emission tomography functional imaging.
OtherFludeoxyglucose F-18
Given IV

Outcome measures

Primary

Sensitivity of metastatic lesion
Defined as the rate of lesions with positive uptake when compared against 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) positivity. Sensitivity estimated based on lesion level without considering the location of the lesions or the possible intracorrelation of the lesions from the same patient by point estimate with its 95% confidence interval.
Time frame: Up to 1 week
Median maximum standardized uptake value (SUVmax)
The median and range of standardized uptake value maximum (SUVmax) (across all metastatic lesions per participant) in each study cohort will be descriptively reported using mediastinal blood pool and normal organ background uptake values.
Time frame: Up to 1 week
Median Standardized Uptake Value averaged across lesions (SUVmax-avg)
The median and range of SUVmax-average across all lesions in each study cohort will be descriptively reported using mediastinal blood pool and normal organ background uptake values.
Time frame: Up to 1 week

Secondary

Proportion of participants reporting treatment-related Adverse Events
Time frame: Up to 35 days
Average organ uptake of [89Zr]DFO-YS5
Time frame: Up to 1 week
Descriptive patterns of intra-tumoral uptake of [89Zr]DFO-YS5
Time frame: Up to 1 week
Dosimetry measurements (Cohort B only)
Time frame: Up to 1 week

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Participants must have histologically or cytologically confirmed multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria * At least one positive myelomatous lesion found on 18F-FDG PET/CT or PET/MRI. A positive lesion is defined as uptake greater than liver on FDG PET, based on the Italian myeloma criteria for PET use (IMPeTUs) criteria * Age \>= 18 years * Total bilirubin =\< 1.5 X institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) =\< 3 X ULN * Alanine aminotransferase (ALT) =\< 3 X ULN * Creatinine clearance \>= 30 mL/min, calculated using the Cockcroft-Gault equation or serum creatinine \<= 1.5x the institutional upper limit of normal. * Ability to understand a written informed consent document, and the willingness to sign it Exclusion Criteria: * Any condition that, in the opinion of the principal investigator, would impair the participants' ability to comply with study procedures or interfere with the safety of the investigational regimen * Individuals who are pregnant or breastfeeding/chestfeeding. * \- Breast-feeding/chest-feeding should be discontinued before administration of \[89ZR\]DFO-YS5. * Females of childbearing potential must have a negative urine or serum pregnancy test (i.e., human chorionic gonadotropin test) within 72 hours prior to administration of \[89ZR\]-DFO-YS5. * \- If the urine pregnancy test is positive or equivocal, a confirmatory serum pregnancy test is required. In such cases, the individual must be excluded from participation if the serum pregnancy result is positive. * \- A female is considered to be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), unless it is documented that the individual meets either of the following two criteria: (1) has reached a postmenopausal state ( \>= 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries). * Individuals who are pregnant or breastfeeding/chestfeeding are excluded because there is an unknown but potential risk for adverse effects in the unborn/nursing child secondary to treatment of the study participant with \[89ZR\]-DFO-YS5

Study locations (1)

University of California, San Francisco

San Francisco, California, 94143

Recruiting

Maya Aslam · Contact

(415) 514-8987 Maya.Aslam@ucsf.edu

· Contact

877-827-3222 cancertrials@ucsf.edu

Robert Flavell, MD, PhD · Principal Investigator