Multiple Myeloma
Conditions
Keywords
89Zr-DFO-daratumumab, CD38-targeting monoclonal antibody, CT, MR, FDG PET/CT, 18-267
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.
Interventions
OTHERBlood 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,
DRUG89Zr-daratumumab
2 mCi of 89Zr-daratumumab will be administered on day 0.
DEVICEPET/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.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody Phase I: Dose Escalation 1-5 mCi in 50mg of antibody | 3 |
| Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody Phase I: Dose Escalation 1-5 mCi in 20mg of antibody | 7 |
| Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody Phase I: Dose Escalation 1-5 mCi in 3-50mg of antibody | 1 |
| Total | 11 |
Baseline characteristics
| Characteristic | Phase I: Dose Escalation 1-5 mCi in 50mg of Antibody | Total | Phase I: Dose Escalation 1-5 mCi in 3-50mg of Antibody | Phase I: Dose Escalation 1-5 mCi in 20mg of Antibody |
|---|---|---|---|---|
| Age, Continuous | 60 years | 59 years | 60 years | 58.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 11 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 8 Participants | 0 Participants | 5 Participants |
| Region of Enrollment United States | 3 Participants | 11 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 7 | 0 / 1 |
| other Total, other adverse events | 2 / 3 | 5 / 7 | 0 / 1 |
| serious Total, serious adverse events | 1 / 3 | 0 / 7 | 0 / 1 |
Outcome results
Primary
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.
Time frame: up to 19 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 89Zr-daratumumab | Average Absorbed Radiation Dose Estimates for Normal Tissues for Phase I Participants | 0.49 mSv/MBq | Standard Error 0.07 |