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

Study Overview
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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.

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

Conditions
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Multiple Myeloma, Plasma Cell Myeloma

Intervention / Treatment
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* 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


Participation Criteria
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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 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 patient's ability to comply with study procedures or interfere with the safety of the investigational regimen Patients who have received the same antibody (YS5) earlier as part of therapy or detection 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A ([89Zr]DFO-YS5, single scan<br>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 | Drug: Zirconium Zr 89-DFO-YS5<br>* Given IV<br>* Other names: 89Zr DFO-YS5;Procedure: Positron Emission Tomography / Computed Tomography (PET/CT)<br>* 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<br>* Other names: PET/CT;Procedure: Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)<br>* 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.<br>* Other names: PET/MRI;Other: Fludeoxyglucose F-18<br>* Given IV<br>* Other names: Fludeoxyglucose (18F);|
| Experimental: Cohort B ([89Zr]DFO-YS5, multiple scans<br>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 | Drug: Zirconium Zr 89-DFO-YS5<br>* Given IV<br>* Other names: 89Zr DFO-YS5;Procedure: Positron Emission Tomography / Computed Tomography (PET/CT)<br>* 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<br>* Other names: PET/CT;Procedure: Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)<br>* 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.<br>* Other names: PET/MRI;Other: Fludeoxyglucose F-18<br>* Given IV<br>* Other names: Fludeoxyglucose (18F);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | Up to 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants reporting treatment-related Adverse Events | Will be reported descriptively using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. | Up to 35 days | 
| Average organ uptake of [89Zr]DFO-YS5 | Regions of interest will be drawn on major organs, and the SUVmax calculated for each patient. Average organ uptake reported with descriptive statistics, including the mean and standard deviation (SD). | Up to 1 week | 
| Descriptive patterns of intra-tumoral uptake of [89Zr]DFO-YS5 | On whole body PET, site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal. The median and range for intra-tumoral SUVmax within metastatic lesions will be reported descriptively on a per-lesion basis to assess for intra-tumoral heterogeneity and differences in uptake by site of disease. | Up to 1 week | 
| Dosimetry measurements (Cohort B only) | Dosimetry calculations will be performed and reported in millisievert (mSv)/megabecquerels (MBq) on a per-patient basis. Time-activity curves will be generated for each organ, and curve-fitting will be performed to derive the time-integrated activity coefficients | Up to 1 week |