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

NCT03665155 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 18-267
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

89Zr-DFO-daratumumab; CD38-targeting monoclonal antibody; CT; MR; FDG PET/CT; 18-267

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

89Zr-daratumumab

EXPERIMENTAL

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; Device: PET/CT scans; Other: Blood draws

Interventions

89Zr-daratumumab DRUG

2 mCi of 89Zr-daratumumab will be administered on day 0.

89Zr-daratumumab

PET/CT scans DEVICE

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.

89Zr-daratumumab

Blood draws OTHER

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,

89Zr-daratumumab

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Slaon-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Positron Emission Tomography Computed Tomography; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Positron-Emission Tomography; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography, X-Ray Computed; Multimodal Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Jason Lewis, PhD
• Organization: Memorial Sloan Kettering Cancer Center

lewisj2@mskcc.org

314-276-1830

Study Officials

• Gary Ulaner, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 11, 2018
• Study Start: September 5, 2018
• Primary Completion: April 20, 2020
• Study Completion: April 20, 2020
• Last Updated: July 30, 2021
• Results First Posted: July 30, 2021

Record last verified: 2021-04

Locations

US (1)