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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03665155
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.5
• Patients Per Site Per Month: 0.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: 89Zr-daratumumab; Device: PET/CT scans; Other: Blood draws	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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.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)
• Primary Purpose: Diagnostic
• Official Title: First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
• Actual Study Start Date: Sep 5, 2018
• Actual Primary Completion Date: Apr 20, 2020
• Actual Study Completion Date: Apr 20, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: 89Zr-daratumumab; 2 mCi of 89Zr-daratumumab will be administered on day 0.; Device: PET/CT scans; 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.; Other: Blood draws; 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,

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Slaon-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Gary Ulaner, MD, PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 20, 2020

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT03665155
• Other Study ID Numbers: 18-267
• First Posted: Sep 11, 2018
• Last Update Posted: Jul 30, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Memorial Sloan Kettering Cancer Center: 89Zr-DFO-daratumumab; CD38-targeting monoclonal antibody; CT; MR; FDG PET/CT; 18-267
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Daratumumab

Study Results

Participant Flow

Recruitment Details	The Phase I portion of the study has concluded. The Phase II portion will not open due to the study PI leaving the institution.

Arm/Group Title	Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody	Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody	Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
Arm/Group Description	Phase I: Dose Escalation 1-5 mCi in 50mg of antibody	Phase I: Dose Escalation 1-5 mCi in 20mg of antibody	Phase I: Dose Escalation 1-5 mCi in 3-50mg of antibody
Period Title: Overall Study
STARTED	3	7	1
COMPLETED	3	7	1
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody	Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody	Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody	Total
Arm/Group Description	Phase I: Dose Escalation 1-5 mCi in 50mg of antibody	Phase I: Dose Escalation 1-5 mCi in 20mg of antibody	Phase I: Dose Escalation 1-5 mCi in 3-50mg of antibody	Total of all reporting groups
Overall Participants	3	7	1	11
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60	58.4	60	59
Sex: Female, Male (Count of Participants)
Female	1 33.3%	2 28.6%	0 0%	3 27.3%
Male	2 66.7%	5 71.4%	1 100%	8 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	7 100%	1 100%	11 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 100%	1 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 14.3%	0 0%	1 9.1%
White	3 100%	5 71.4%	0 0%	8 72.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 14.3%	0 0%	1 9.1%
Region of Enrollment (Count of Participants)
United States	3 100%	7 100%	1 100%	11 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	89Zr-daratumumab
Arm/Group Description	The Phase I portion of the study has concluded. The Phase II portion has not yet opened to accrual.
Measure Participants	11
Mean (Standard Error) [mSv/MBq]	0.49 (0.07)

Adverse Events

Time Frame	approximately 1 year 7 months
Arm/Group Title	Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
Arm/Group 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).		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).		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).
All Cause Mortality
	Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/7 (28.6%)		0/1 (0%)
Serious Adverse Events
	Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Cardiac disorders
Sinus tachycardia	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
General disorders
Chills	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Immune system disorders
Allergic reaction	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody		Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		5/7 (71.4%)		0/1 (0%)
Blood and lymphatic system disorders
Anemia	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Investigations
Lymphocyte count decreased	2/3 (66.7%)		4/7 (57.1%)		0/1 (0%)
Neutrophil count decreased	2/3 (66.7%)		2/7 (28.6%)		0/1 (0%)
White blood cell decreased	2/3 (66.7%)		2/7 (28.6%)		0/1 (0%)
Aspartate aminotransferase increased	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Blood bilirubin increased	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Creatinine increased	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Platelet count decreased	1/3 (33.3%)		0/7 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Hyperglycemia	1/3 (33.3%)		0/7 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.