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

Phase 1

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: 89Zr-daratumumab; Device: PET/CT scans; Other: Blood draws

• Registration Number: NCT03665155
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2018-09-05
• Study First Submitted: 2018-09-06
• Study First Submitted QC: 2018-09-07
• Study First Posted: 2018-09-11
• Primary Completion: 2020-04-20
• Study Completion: 2020-04-20
• Results First Submitted: 2020-11-20
• Status Verified: 2021-04
• Results First Submitted QC: 2021-07-09
• Last Update Submitted: 2021-07-09
• Results First Posted: 2021-07-30
• Last Update Posted: 2021-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
89Zr-daratumumab	89Zr-daratumumab	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.
89Zr-daratumumab	PET/CT scans	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.
89Zr-daratumumab	Blood draws	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.

Primary Outcome Measures

Name	Time	Method
Average Absorbed Radiation Dose Estimates for Normal Tissues for Phase I Participants	up to 19 months	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.

Trial Locations

Locations (1)

Memorial Slaon-Kettering Cancer Center; 🇺🇸 New York, New York, United States