Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma
- Conditions
- Multiple MyelomaPlasma Cell Myeloma
- Interventions
- Procedure: Positron Emission Tomography / Computed Tomography (PET/CT)Procedure: Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)Other: Fludeoxyglucose F-18
- Registration Number
- NCT05892393
- Lead Sponsor
- Robert Flavell, MD, PhD
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- 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
- 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.
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- 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.
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- 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.
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- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort A ([89Zr]DFO-YS5, single scan Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI) 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 Cohort A ([89Zr]DFO-YS5, single scan Fludeoxyglucose F-18 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 Cohort A ([89Zr]DFO-YS5, single scan Zirconium Zr 89-DFO-YS5 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 Cohort A ([89Zr]DFO-YS5, single scan Positron Emission Tomography / Computed Tomography (PET/CT) 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 Cohort B ([89Zr]DFO-YS5, multiple scans Positron Emission Tomography / Computed Tomography (PET/CT) 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 Cohort B ([89Zr]DFO-YS5, multiple scans Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI) 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 Cohort B ([89Zr]DFO-YS5, multiple scans Fludeoxyglucose F-18 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 Cohort B ([89Zr]DFO-YS5, multiple scans Zirconium Zr 89-DFO-YS5 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
- Primary Outcome Measures
Name Time Method Median Standardized Uptake Value averaged across lesions (SUVmax-avg) Up to 1 week 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.
Sensitivity of metastatic lesion Up to 1 week 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.
Median maximum standardized uptake value (SUVmax) Up to 1 week 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.
- Secondary Outcome Measures
Name Time Method Average organ uptake of [89Zr]DFO-YS5 Up to 1 week 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).
Proportion of participants reporting treatment-related Adverse Events Up to 35 days Will be reported descriptively using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Descriptive patterns of intra-tumoral uptake of [89Zr]DFO-YS5 Up to 1 week 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.
Dosimetry measurements (Cohort B only) Up to 1 week 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
Trial Locations
- Locations (1)
University of California, San Francisco
🇺🇸San Francisco, California, United States