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

Robert Flavell, MD, PhD

Status and phase: Enrolling; Phase 1

Conditions: Plasma Cell Myeloma; Multiple Myeloma

Treatments: Drug: Zirconium Zr 89-DFO-YS5; Procedure: Positron Emission Tomography / Computed Tomography (PET/CT); Procedure: Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI); Other: Fludeoxyglucose F-18

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05892393

R01CA271606 (U.S. NIH Grant/Contract)

NCI-2023-04068 (Registry Identifier)

23925

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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
• 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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

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

Experimental group

Description:

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

Treatment:

Other: Fludeoxyglucose F-18

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

Procedure: Positron Emission Tomography / Computed Tomography (PET/CT)

Drug: Zirconium Zr 89-DFO-YS5

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

Experimental group

Description:

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

Treatment:

Other: Fludeoxyglucose F-18

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

Procedure: Positron Emission Tomography / Computed Tomography (PET/CT)

Drug: Zirconium Zr 89-DFO-YS5