Back to resultsImaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma
Primary Purpose
Multiple Myeloma, Plasma Cell Myeloma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Zirconium Zr 89-DFO-YS5
Positron Emission Tomography / Computed Tomography (PET/CT)
Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)
Fludeoxyglucose F-18
Sponsored by
About this trial
This is an interventional diagnostic trial for Multiple Myeloma
Eligibility Criteria
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
Sites / Locations
- University of California, San FranciscoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A ([89Zr]DFO-YS5, single scan
Cohort B ([89Zr]DFO-YS5, multiple scans
Arm 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
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
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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).
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.
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
Full Information
NCT ID
NCT05892393
First Posted
May 26, 2023
Last Updated
July 5, 2023
Sponsor
Robert Flavell, MD, PhD
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT05892393
Brief Title
Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma
Official Title
Pilot PET Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 16, 2023 (Actual)
Primary Completion Date
August 1, 2026 (Anticipated)
Study Completion Date
September 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robert Flavell, MD, PhD
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Plasma Cell Myeloma
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort A ([89Zr]DFO-YS5, single scan
Arm Type
Experimental
Arm 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
Arm Title
Cohort B ([89Zr]DFO-YS5, multiple scans
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Zirconium Zr 89-DFO-YS5
Other Intervention Name(s)
(89)Zr-DFO-YS5, 89Zr DFO-YS5
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography / Computed Tomography (PET/CT)
Other Intervention Name(s)
PET/CT
Intervention Description
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
Intervention Name(s)
Positron Emission Tomography / Magnetic Resonance Imaging (PET/MRI)
Other Intervention Name(s)
PET/MRI
Intervention Description
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
Other
Intervention Name(s)
Fludeoxyglucose F-18
Other Intervention Name(s)
Fludeoxyglucose (18F)
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Sensitivity of metastatic lesion
Description
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
Title
Median maximum standardized uptake value (SUVmax)
Description
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
Title
Median Standardized Uptake Value averaged across lesions (SUVmax-avg)
Description
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 Outcome Measure Information:
Title
Proportion of participants reporting treatment-related Adverse Events
Description
Will be reported descriptively using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time Frame
Up to 35 days
Title
Average organ uptake of [89Zr]DFO-YS5
Description
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).
Time Frame
Up to 1 week
Title
Descriptive patterns of intra-tumoral uptake of [89Zr]DFO-YS5
Description
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.
Time Frame
Up to 1 week
Title
Dosimetry measurements (Cohort B only)
Description
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
Time Frame
Up to 1 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maya Aslam
Phone
(415) 514-8987
Email
Maya.Aslam@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Flavell, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maya Aslam
Phone
415-514-8987
Email
Maya.Aslam@ucsf.edu
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Robert Flavell, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma
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