Back to resultsFirst-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
89Zr-daratumumab
PET/CT scans
Blood draws
Sponsored by
About this trial
This is an interventional diagnostic trial for Multiple Myeloma focused on measuring 89Zr-DFO-daratumumab, CD38-targeting monoclonal antibody, CT, MR, FDG PET/CT, 18-267
Eligibility Criteria
Inclusion Criteria:
- Age 21 years or greater
- Histologically/Immunohistochemistry confirmed CD38-positive multiple myeloma
- At least one tumor lesion on CT, MRI, or FDG PET/CT within 60 days of protocol enrollment
- ECOG performance status 0 to 2
- For Phase II patients only: plan for initiation of standard-of-care daratumumab/lenalidomide therapy.
Exclusion Criteria:
- Life expectancy < 3 months
- Pregnancy or lactation
- Patients who cannot undergo PET/CT scanning because of weight limits. PET/CT scanners may not be able to function with patients over 450 pounds.
- History of anaphylactic reaction to humanized or human antibodies or a Grade 3 or 4 administration reaction during a daratumumab administration.
Sites / Locations
- Memorial Slaon-Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
89Zr-daratumumab
Arm Description
Three patients will be administered 2 mCi of 89Zr-daratumumab in a total of 50 mg of daratumumab antibody. Administered activity (1 to 5 mCi) of radioactivity and total amount of administered antibody (3 to 50 mg) will be adjusted in subsequent patients in order to maximize image quality. Patients in phase I will have up to 4 PET/CT scans, multiple blood draws, whole-body counts, and safety monitoring to determine pharmacokinetics, radiation dosimetry, and safety of 89Zr-DFO-daratumumab for PET/CT imaging. Phase II (total of 21-24 patients). After pharmacokinetics and radiation dosimetry are determined in phase I, additional patients will be enrolled in phase II.
Outcomes
Primary Outcome Measures
Average Absorbed Radiation Dose Estimates for Normal Tissues for Phase I Participants
Standardized uptake value (SUV) in various organs will be estimated from VOI analysis of clinical images and converted to activity-time curves. The areas under the activity-time curves will be derived by integration, converted to residence times, and used as input to the OLINDA/EXM dosimetry program to obtain absorbed dose estimates for normal tissues for all Phase I participants, regardless of study dose. Each participant underwent four PET/CT scans over the next 8 days, as well as blood chemistry and whole-body counts, to determine safety, tracer biodistribution, pharmacokinetics, and radiation dosimetry. Because 89Zr has a half-life of 78 hours, only a single administration of tracer was needed to obtain all four PET/CT scans for all Phase I participants. Results were combined because all received the same dose of tracer.
Secondary Outcome Measures
Full Information
NCT ID
NCT03665155
First Posted
September 6, 2018
Last Updated
July 9, 2021
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT03665155
Brief Title
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
Official Title
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
September 5, 2018 (Actual)
Primary Completion Date
April 20, 2020 (Actual)
Study Completion Date
April 20, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to test 89Zr-DFO-daratumumab, a new imaging agent, to demonstrate its safety and ability to take pictures of the myeloma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
89Zr-DFO-daratumumab, CD38-targeting monoclonal antibody, CT, MR, FDG PET/CT, 18-267
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is a phase I/II study with the goal to assess the feasibility of using the anti-CD38 monoclonal antibody daratumumab, labeled with Zirconium-89 (89Zr ) through deferoxamine (DFO), known as 89Zr-DFO-daratumumab, for PET imaging of multiple myeloma.
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
89Zr-daratumumab
Arm Type
Experimental
Arm Description
Three patients will be administered 2 mCi of 89Zr-daratumumab in a total of 50 mg of daratumumab antibody. Administered activity (1 to 5 mCi) of radioactivity and total amount of administered antibody (3 to 50 mg) will be adjusted in subsequent patients in order to maximize image quality.
Patients in phase I will have up to 4 PET/CT scans, multiple blood draws, whole-body counts, and safety monitoring to determine pharmacokinetics, radiation dosimetry, and safety of 89Zr-DFO-daratumumab for PET/CT imaging. Phase II (total of 21-24 patients). After pharmacokinetics and radiation dosimetry are determined in phase I, additional patients will be enrolled in phase II.
Intervention Type
Drug
Intervention Name(s)
89Zr-daratumumab
Intervention Description
2 mCi of 89Zr-daratumumab will be administered on day 0.
Intervention Type
Device
Intervention Name(s)
PET/CT scans
Intervention Description
PET/CT images will be obtained on post-administration days 1, 2-4, 5-6, and/or 7-8 following administration of 89Zr-DFO-daratumumab to determine the optimal time point for imaging.
Intervention Type
Other
Intervention Name(s)
Blood draws
Intervention Description
Blood and serum samples will be weighed and counted in a scintillation well counter calibrated for 89Zr. Immediately before or after each PET/CT imaging session,
Primary Outcome Measure Information:
Title
Average Absorbed Radiation Dose Estimates for Normal Tissues for Phase I Participants
Description
Standardized uptake value (SUV) in various organs will be estimated from VOI analysis of clinical images and converted to activity-time curves. The areas under the activity-time curves will be derived by integration, converted to residence times, and used as input to the OLINDA/EXM dosimetry program to obtain absorbed dose estimates for normal tissues for all Phase I participants, regardless of study dose. Each participant underwent four PET/CT scans over the next 8 days, as well as blood chemistry and whole-body counts, to determine safety, tracer biodistribution, pharmacokinetics, and radiation dosimetry. Because 89Zr has a half-life of 78 hours, only a single administration of tracer was needed to obtain all four PET/CT scans for all Phase I participants. Results were combined because all received the same dose of tracer.
Time Frame
up to 19 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 21 years or greater
Histologically/Immunohistochemistry confirmed CD38-positive multiple myeloma
At least one tumor lesion on CT, MRI, or FDG PET/CT within 60 days of protocol enrollment
ECOG performance status 0 to 2
For Phase II patients only: plan for initiation of standard-of-care daratumumab/lenalidomide therapy.
Exclusion Criteria:
Life expectancy < 3 months
Pregnancy or lactation
Patients who cannot undergo PET/CT scanning because of weight limits. PET/CT scanners may not be able to function with patients over 450 pounds.
History of anaphylactic reaction to humanized or human antibodies or a Grade 3 or 4 administration reaction during a daratumumab administration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Ulaner, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Slaon-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
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