Trial Outcomes & Findings for First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody (NCT NCT03665155)
NCT ID: NCT03665155
Last Updated: 2021-07-30
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
11 participants
Primary outcome timeframe
up to 19 months
Results posted on
2021-07-30
Participant Flow
The Phase I portion of the study has concluded. The Phase II portion will not open due to the study PI leaving the institution.
Participant milestones
| Measure |
Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody
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 20mg of antibody
|
Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
Phase I: Dose Escalation 1-5 mCi in 3-50mg of antibody
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
7
|
1
|
|
Overall Study
COMPLETED
|
3
|
7
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
Baseline characteristics by cohort
| Measure |
Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody
n=3 Participants
Phase I: Dose Escalation 1-5 mCi in 50mg of antibody
|
Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody
n=7 Participants
Phase I: Dose Escalation 1-5 mCi in 20mg of antibody
|
Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
n=1 Participants
Phase I: Dose Escalation 1-5 mCi in 3-50mg of antibody
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60 years
n=93 Participants
|
58.4 years
n=4 Participants
|
60 years
n=27 Participants
|
59 years
n=483 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
11 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
3 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
11 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: up to 19 monthsStandardized 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.
Outcome measures
| Measure |
89Zr-daratumumab
n=11 Participants
The Phase I portion of the study has concluded. The Phase II portion has not yet opened to accrual.
|
|---|---|
|
Average Absorbed Radiation Dose Estimates for Normal Tissues for Phase I Participants
|
0.49 mSv/MBq
Standard Error 0.07
|
Adverse Events
Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody
Serious events: 1 serious events
Other events: 2 other events
Deaths: 2 deaths
Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody
Serious events: 0 serious events
Other events: 5 other events
Deaths: 2 deaths
Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody
n=3 participants at risk
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).
|
Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody
n=7 participants at risk
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).
|
Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
n=1 participants at risk
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).
|
|---|---|---|---|
|
Immune system disorders
Allergic reaction
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
General disorders
Chills
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Cardiac disorders
Sinus tachycardia
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
Other adverse events
| Measure |
Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody
n=3 participants at risk
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).
|
Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody
n=7 participants at risk
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).
|
Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody
n=1 participants at risk
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).
|
|---|---|---|---|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • approximately 1 year 7 months
|
57.1%
4/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Investigations
Neutrophil count decreased
|
66.7%
2/3 • approximately 1 year 7 months
|
28.6%
2/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Investigations
White blood cell decreased
|
66.7%
2/3 • approximately 1 year 7 months
|
28.6%
2/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Investigations
Blood bilirubin increased
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Investigations
Creatinine increased
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
|
Investigations
Platelet count decreased
|
33.3%
1/3 • approximately 1 year 7 months
|
0.00%
0/7 • approximately 1 year 7 months
|
0.00%
0/1 • approximately 1 year 7 months
|
Additional Information
Jason Lewis, PhD
Memorial Sloan Kettering Cancer Center
Phone: 314-276-1830
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place