Radioactive Tracer Imaging for Multiple Myeloma

Overseen By Maya Aslam

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Robert Flavell, MD, PhD

Disqualifiers: Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 week

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety of \[89Zr\]DFO-YS5 positron emission tomography (PET) imaging and how well it works to detect CD46 positive cancer cells in patients with multiple myeloma. \[89Zr\]DFO-YS5 is an imaging agent called a radiopharmaceutical tracer. A radiopharmaceutical tracer uses a small amount of radioactive material that is injected into a vein to help image different areas of the body. \[89Zr\]DFO-YS5 targets a specialized protein called CD46, which is in certain multiple myeloma cancer cells, and \[89Zr\]DFO-YS5 PET scans may improve detection of multiple myeloma.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Zirconium Zr 89-DFO-YS5 for multiple myeloma?

Research on similar treatments, like Zirconium-89 labeled antibodies, shows promise in effectively imaging multiple myeloma by targeting specific markers on cancer cells, which helps in identifying disease activity and monitoring treatment response. ^{1 2 3 4 5}

Is Zirconium Zr 89-DFO-YS5 safe for use in humans?

In a study involving 10 patients with multiple myeloma, the use of 89Zr-DFO-daratumumab, a similar radioactive tracer, was found to be safe with acceptable radiation levels. This suggests that similar tracers like Zirconium Zr 89-DFO-YS5 may also be safe for human use. ^{1 2 3 6 7}

How does the radioactive tracer imaging treatment for multiple myeloma differ from other treatments?

This treatment uses radioactive tracers to specifically target and visualize active multiple myeloma lesions, unlike traditional imaging methods that struggle to differentiate between old and new lesions. It leverages the CD38 biomarker, which is highly expressed in myeloma cells, allowing for precise imaging and potentially guiding therapy decisions. ^{1 2 3 8 9}

Research Team

Robert Flavell, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with confirmed multiple myeloma, who have at least one lesion visible on PET scans. They must have normal bilirubin levels, a creatinine clearance of >=60 mL/min, and liver enzymes (AST/ALT) within three times the upper limit. Pregnant or breastfeeding individuals are excluded, as well as those unable to follow study procedures.

Inclusion Criteria

Your alanine aminotransferase (ALT) blood level is less than or equal to three times the upper limit of normal.

My scans show at least one active cancer lesion, more intense than the liver.

My kidneys are functioning well, with a creatinine clearance rate of 60 mL/min or higher.

Exclusion Criteria

I have previously received treatment or testing involving the YS5 antibody.

I am not pregnant or breastfeeding.

I am not pregnant or breastfeeding and have had a negative pregnancy test in the last 72 hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive [89Zr]DFO-YS5 IV and undergo PET/CT or PET/MRI scans to detect CD46 positive cancer cells

1 week

1-4 visits (in-person) depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Zirconium Zr 89-DFO-YS5

Trial Overview [89Zr]DFO-YS5 PET imaging is being tested for its ability to detect CD46 positive cancer cells in multiple myeloma patients. This phase I trial will assess the safety of this radiopharmaceutical tracer and its effectiveness in improving detection of the disease.

Participant Groups

Group I: Cohort B ([89Zr]DFO-YS5, multiple scans Experimental Treatment 4 Interventions

Participants receive \[89Zr\]DFO-YS5 IV and undergo four PET/CT or PET/MRI scans on days 1, 2, 3-4, and 5-7 post-injection. Participants also receive fludeoxyglucose F-18 IV and undergo PET/CT or PET/MRI scan within 28 days prior to day 1

Group II: Cohort A ([89Zr]DFO-YS5, single scan Experimental Treatment 4 Interventions

Participants receive \[89Zr\]DFO-YS5 IV and undergo a single PET/CT or PET/MRI scan 5-7 days post-injection. Participants also receive fludeoxyglucose F-18 IV and undergo PET/CT or PET/MRI scan within 28 days prior to day 1

Who Is Running the Clinical Trial?

Robert Flavell, MD, PhD

Lead Sponsor

Trials

5

Recruited

90+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Modern imaging techniques like magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT) are more effective than whole-body X-ray (WBX) for detecting active multiple myeloma (MM) lesions, which is crucial for monitoring disease progression.

Nuclear imaging using radiopharmaceuticals can specifically target malignant plasma cells, offering promising results for staging and monitoring treatment response in relapsing MM patients, and some tracers may even be applicable for radioimmunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting. de Waal, EGM., Glaudemans, AWJM., Schröder, CP., et al.[2019]

The study developed a novel immunoPET tracer using Zirconium-89-labeled isatuximab, which targets CD38, a biomarker highly expressed in multiple myeloma (MM) and certain lymphomas, showing high binding affinity and specificity in vitro.

PET imaging with this tracer effectively delineated tumor burden in models of MM and Burkitt's lymphoma, indicating its potential as a noninvasive imaging agent to improve diagnosis and treatment monitoring in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-DFO-Isatuximab for CD38-Targeted ImmunoPET Imaging of Multiple Myeloma and Lymphomas. Herrero Alvarez, N., Michel, AL., Viray, TD., et al.[2023]

The study successfully developed 89Zr-DFO-daratumumab, a radiolabeled monoclonal antibody that targets CD38 on multiple myeloma cells, showing high radiochemical purity and specificity in preclinical models.

In a phase I trial with 10 patients, 89Zr-DFO-daratumumab was found to be safe and effective for immunologic PET imaging, allowing visualization of myeloma sites in the bone, which could improve disease burden assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38-targeted Immuno-PET of Multiple Myeloma: From Xenograft Models to First-in-Human Imaging. Ulaner, GA., Sobol, NB., O'Donoghue, JA., et al.[2021]

PET/CT using the tracer 18F-FDG is a powerful diagnostic tool for multiple myeloma, effectively detecting both medullary and extramedullary disease, and is a reliable predictor of patient survival and treatment response.

Despite its advantages, 18F-FDG has limitations, such as poor sensitivity for diffuse bone marrow infiltration and low specificity, prompting the exploration of alternative PET tracers that may improve detection of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma. Sachpekidis, C., Goldschmidt, H., Dimitrakopoulou-Strauss, A.[2020]

In a study of 18 patients with multiple myeloma, higher uptake of F-18 fluorodeoxyglucose (FDG) in the bone marrow was significantly associated with more aggressive disease and shorter survival, indicating its prognostic value.

FDG uptake was found to be comparable to Tc-99m methoxy-isobutyl-isonitrile (MIBI) uptake in predicting disease severity, suggesting that FDG imaging should be included in initial assessments of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prognostic value of F-18 fluorodeoxyglucose bone marrow uptake in patients with recent diagnosis of multiple myeloma: a comparative study with Tc-99m sestamibi. Castellani, M., Carletto, M., Baldini, L., et al.[2019]

In a study using a mouse model of multiple myeloma, the anti-CD138 antibody labeled with copper-64 (64Cu) showed optimal tumor-to-nontarget tissue ratios, making it a promising candidate for PET imaging in humans.

Compared to the standard 18F-FDG PET imaging, both 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 demonstrated higher uptake in bone lesions, with 64Cu-TE2A-9E7.4 providing better specificity and less nonspecific bone uptake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model. Bailly, C., Gouard, S., Guérard, F., et al.[2020]

The novel chelator DFOcyclo* demonstrated significantly higher stability in both in vitro and in vivo settings compared to the commonly used DFO, particularly in the presence of competing agents like EDTA and DFO, making it a more reliable option for 89Zr labeling.

In vivo studies showed that DFOcyclo*-trastuzumab resulted in lower bone uptake of 89Zr, which is beneficial as it reduces unwanted accumulation in bone tissue, while maintaining similar blood levels and tumor uptake compared to DFO-trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET. Raavé, R., Sandker, G., Adumeau, P., et al.[2020]

A new CD38-targeted radiotracer, [18F]F-Nb1053, was developed using bioorthogonal click chemistry and showed high radiochemical purity and excellent immunoreactivity for diagnosing multiple myeloma (MM).

ImmunoPET imaging with [18F]F-Nb1053 effectively identified MM lesions in preclinical models, demonstrating its potential to improve the management of MM, especially as tumor uptake decreased after daratumumab treatment, indicating its specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Annotating CD38 Expression in Multiple Myeloma with [18F]F-Nb1053. Wei, W., Zhang, D., Wang, C., et al.[2022]

In a study involving 28 patients with multiple myeloma and solitary plasmacytoma, the use of 67Ga-citrate for total-body scans showed effective localization, particularly when compared to other agents like 99mTc-diphosphonate and 99mTc-polyphosphate.

The rare-earth agent 157Dy demonstrated comparable localization to 99mTc-PP and 99mTc-DP, and it was particularly useful for imaging the abdomen and pelvis due to its minimal gastrointestinal concentration, with no observed toxic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of rare-earth radionuclides and other bone-seekers in the evaluation of bone lesions in patients with multiple myeloma or solitary plasmacytoma. Hubner, KF., Andrews, GA., Hayes, RL., et al.[2015]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

89Zr-DFO-Isatuximab for CD38-Targeted ImmunoPET Imaging of Multiple Myeloma and Lymphomas. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

CD38-targeted Immuno-PET of Multiple Myeloma: From Xenograft Models to First-in-Human Imaging. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

The prognostic value of F-18 fluorodeoxyglucose bone marrow uptake in patients with recent diagnosis of multiple myeloma: a comparative study with Tc-99m sestamibi. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Annotating CD38 Expression in Multiple Myeloma with [18F]F-Nb1053. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The use of rare-earth radionuclides and other bone-seekers in the evaluation of bone lesions in patients with multiple myeloma or solitary plasmacytoma. [2015]