First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody

Study Overview
=================
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.

Official Title
-----------------
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: 89Zr-daratumumab
* Device: PET/CT scans
* Other: Blood draws


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 89Zr-daratumumab<br>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. | Drug: 89Zr-daratumumab<br>* 2 mCi of 89Zr-daratumumab will be administered on day 0.<br>Device: PET/CT scans<br>* 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.<br>Other: Blood draws<br>* 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,<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 19 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
89Zr-DFO-daratumumab, CD38-targeting monoclonal antibody, CT, MR, FDG PET/CT, 18-267