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

NCT ID: NCT05892393

Last Updated: 2025-11-12

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

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-16

Study Completion Date

2026-09-01

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma Plasma Cell Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Cohort A ([89Zr]DFO-YS5, single scan

Participants receive \[89Zr\]DFO-YS5 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

Group Type EXPERIMENTAL

Zirconium Zr 89-DFO-YS5

Intervention Type DRUG

Given IV

Positron Emission Tomography / Computed Tomography (PET/CT)

Intervention Type PROCEDURE

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

Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)

Intervention Type PROCEDURE

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.

Fludeoxyglucose F-18

Intervention Type OTHER

Given IV

Cohort B ([89Zr]DFO-YS5, multiple scans

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

Group Type EXPERIMENTAL

Zirconium Zr 89-DFO-YS5

Intervention Type DRUG

Given IV

Positron Emission Tomography / Computed Tomography (PET/CT)

Intervention Type PROCEDURE

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

Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)

Intervention Type PROCEDURE

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.

Fludeoxyglucose F-18

Intervention Type OTHER

Given IV

Interventions

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Zirconium Zr 89-DFO-YS5

Given IV

Intervention Type DRUG

Positron 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

Intervention Type PROCEDURE

Positron 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.

Intervention Type PROCEDURE

Fludeoxyglucose F-18

Given IV

Intervention Type OTHER

Other Intervention Names

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(89)Zr-DFO-YS5 89Zr DFO-YS5 PET/CT PET/MRI Fludeoxyglucose (18F)

Eligibility Criteria

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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 \>= 60 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Robert Flavell, MD, PhD

OTHER

Sponsor Role lead

Responsible Party

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Robert Flavell, MD, PhD

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Robert Flavell, MD, PhD

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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Maya Aslam

Role: CONTACT

(415) 514-8987

Facility Contacts

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Maya Aslam

Role: primary

(415) 514-8987

Role: backup

877-827-3222

Other Identifiers

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NCI-2023-04068

Identifier Type: REGISTRY

Identifier Source: secondary_id

R01CA271606

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23925

Identifier Type: -

Identifier Source: org_study_id

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