ImmunoPET Imaging for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Beth Thomsen, CNMT

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoag Memorial Hospital Presbyterian

Disqualifiers: Pregnant, Life expectancy < 12 months, Anaphylactic reaction, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 12 cycles

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Evaluation of myeloma disease burden is currently suboptimal. This limits treatment planning and evaluation of residual disease following treatment. 89Zr-DFO-daratumumab is a novel immunoPET tracer, designed to detect CD38 on myeloma cells and allow visualization of myeloma in a PET scanner. A phase I study of 89Zr-DFO-daratumumab demonstrated safety and successful visualization of myeloma with 89Zr-DFO-daratumumab. This will be a phase II study of 89Zr-DFO-daratumumab to evaluate potential clinical applications of this novel imaging agent.

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

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug 89Zr-daratumumab PET/CT for multiple myeloma?

Research shows that 89Zr-daratumumab PET/CT is effective in targeting CD38, a protein found on myeloma cells, allowing for precise imaging of multiple myeloma in both animal models and humans. This drug demonstrated high specificity and sensitivity in detecting myeloma tumors, making it a promising tool for imaging and potentially guiding treatment. ^{1 2 3 4 5}

Is 89Zr-DFO-daratumumab safe for use in humans?

In a study involving 10 patients with multiple myeloma, 89Zr-DFO-daratumumab was found to be safe with acceptable radiation levels. The study showed that it could be used for imaging without significant safety concerns. ^{1 2 6 7 8}

How does ImmunoPET imaging for multiple myeloma differ from other treatments?

ImmunoPET imaging for multiple myeloma is unique because it uses a radiolabeled antibody, 89Zr-DFO-daratumumab, to specifically target and visualize CD38, a protein found on myeloma cells, allowing for precise imaging of the disease. This approach differs from traditional treatments as it focuses on imaging rather than directly treating the cancer, providing a non-invasive method to monitor disease progression and response to therapy. ^{1 2 4 9 10}

Research Team

Leila Andreas, MS

Principal Investigator

Hoag Memorial Hospital Presbyterian

Eligibility Criteria

This trial is for adults over 21 with confirmed CD38-positive multiple myeloma, who have at least one tumor visible on recent scans and can follow the study's procedures. It's not for pregnant or breastfeeding individuals, those not using birth control, patients expected to live less than a year, or anyone too heavy for PET/CT scanners.

Inclusion Criteria

Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

You need to have at least one visible tumor on a recent CT, MRI, or PET scan.

My multiple myeloma is CD38 positive.

Exclusion Criteria

You are not expected to live for another year.

You had a severe allergic reaction to humanized or human antibodies in the past.

You weigh more than 450 pounds and may not fit in the PET/CT scanner.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Evaluation

Participants undergo standard of care diagnostic tests and experimental 89Zr-daratumumab PET/CT imaging

1-2 weeks

1 visit (in-person)

Treatment

Participants receive standard of care therapy for multiple myeloma as defined by a medical oncologist

12 cycles

Post-treatment Evaluation

Participants repeat standard of care diagnostic tests and experimental 89Zr-daratumumab PET/CT imaging to assess response

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

Treatment Details

Interventions

• 89Zr-daratumumab PET/CT

Trial Overview The trial tests an imaging agent called 89Zr-DFO-daratumumab in a PET scanner to visualize myeloma cells. This phase II study aims to assess how well it works and its potential clinical uses after showing safety and effectiveness in an earlier phase I trial.

Participant Groups

Group I: CD38-positive multiple myeloma Experimental Treatment 1 Intervention

Patients with CD38 positive multiple myeloma with be enrolled. Patients will undergo pretreatment evaluation with standard of care diagnostic tests, as well as experimental 89Zr-daratumumab PET/CT. Patients will then undergo a course of standard of care therapy as defined by a medical oncologist. Following therapy, patients will repeat standard of care diagnostic tests, as well as experimental 89Zr-daratumumab PET/CT. Data analysis will be performed to evaluate 89Zr-daratumumab against standard of care diagnostic tests for the detection and localization of active disease before and after therapy.

Who Is Running the Clinical Trial?

Hoag Memorial Hospital Presbyterian

Lead Sponsor

Trials

37

Recruited

17,200+

Findings from Research

Daratumumab, a monoclonal antibody targeting CD38, shows high specificity and sensitivity in imaging multiple myeloma tumors using [89Zr]Zr-DFO-daratumumab PET/CT, effectively detecting tumors of various sizes.

The study demonstrated that [89Zr]Zr-DFO-daratumumab has a strong binding affinity to CD38+ myeloma cells, with a dissociation constant of 3.3 nM, indicating its potential for image-guided delivery of therapeutic radionuclides in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Development of CD38-Targeted [89Zr]Zr-DFO-Daratumumab for Imaging Multiple Myeloma. Ghai, A., Maji, D., Cho, N., et al.[2022]

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]

In a study of 41 patients with multiple myeloma and amyloidosis treated with daratumumab, those in second-line therapy and with advanced amyloidosis showed high rates of durable responses, while advanced multiple myeloma patients had a low overall response rate of only 36%.

The study found that daratumumab's effectiveness was particularly poor in patients with extramedullary plasmacytomas, and the results suggest that daratumumab should be administered earlier in the treatment course for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis. Pick, M., Vainstein, V., Goldschmidt, N., et al.[2018]

The study demonstrated that 89Zr-labeled daratumumab can effectively differentiate CD38 expression in lymphoma models, showing high tumor uptake in CD38-positive cells, which suggests its potential as a non-invasive imaging agent for monitoring multiple myeloma.

ImmunoPET imaging revealed significant differences in CD38 expression between lymphoma cell lines, with the Ramos cell line showing the highest uptake of the imaging agent, indicating that this method could be useful for assessing prognosis and treatment response in hematological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled daratumumab. Kang, L., Jiang, D., England, CG., et al.[2019]

In a study of 178 multiple myeloma patients who progressed after daratumumab treatment, the median progression-free survival (PFS) was only 4.5 months and overall survival (OS) was 14.2 months, indicating limited effectiveness of subsequent therapies.

Patients receiving pomalidomide-based therapy had a slightly better median PFS and OS (5.2 months and 21.7 months, respectively) compared to those on carfilzomib-based therapy, highlighting the need for new treatment options for patients previously treated with daratumumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis. LeBlanc, R., Mian, H., Reece, D., et al.[2023]

In a study of 99 Hungarian patients with relapsed/refractory multiple myeloma, daratumumab demonstrated an overall response rate of 88%, with a median progression-free survival (PFS) of 17.0 months, indicating its efficacy in a real-world setting.

The treatment was generally safe, with mild infusion reactions and hematologic toxicities being the most common side effects, and it was effective even in patients with impaired renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on the efficacy and safety of daratumumab treatment in Hungarian relapsed/refractory multiple myeloma patients. Lovas, S., Varga, G., Farkas, P., et al.[2020]

Daratumumab, now available in a subcutaneous form, significantly reduces administration time from 7 hours to just 3-5 minutes compared to the intravenous version, making it more convenient for patients.

The subcutaneous formulation also has lower rates of infusion-related reactions (less than 10% compared to 50% for intravenous), while maintaining similar efficacy and safety profiles, which enhances its overall usability in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. Sanchez, L., Richter, J., Cho, HJ., et al.[2021]

The Phase II PLEIADES study demonstrated that subcutaneous daratumumab (DARA SC) combined with standard treatments for multiple myeloma achieved high response rates, with ≥very good partial response (VGPR) rates of 71.6% for transplant-eligible patients and overall response rates of 88.1% and 90.8% for transplant-ineligible and relapsed/refractory patients, respectively.

DARA SC was associated with low rates of infusion-related reactions (≤9.0%) and significantly reduced administration time (median of 5 minutes), making it a convenient and effective alternative to intravenous daratumumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label Phase II study. Chari, A., Rodriguez-Otero, P., McCarthy, H., et al.[2021]

Daratumumab (DAR) demonstrated significant anti-tumor effects in a mouse model of multiple myeloma, indicating its efficacy as a treatment for this cancer.

The mechanism of action for DAR includes inducing antibody-dependent cellular phagocytosis (ADCP) through interactions with macrophages, specifically via Fc-FcγR interactions, which enhances the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody Daratumumab promotes macrophage-mediated anti-myeloma phagocytic activity via engaging FC gamma receptor and activation of macrophages. Gao, Y., Li, L., Zheng, Y., et al.[2022]

The phase 1 trial demonstrated that 64Cu-daratumumab PET/CT is a safe imaging technique for detecting multiple myeloma, with no significant adverse events reported in 12 patients.

Using 45 mg of unlabeled daratumumab improved image quality by reducing background signal, suggesting that 64Cu-daratumumab may offer better sensitivity and specificity compared to traditional FDG PET/CT for identifying multiple myeloma lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab. Krishnan, A., Adhikarla, V., Poku, EK., et al.[2022]

References

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

Preclinical Development of CD38-Targeted [89Zr]Zr-DFO-Daratumumab for Imaging Multiple Myeloma. [2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled daratumumab. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

Real-world data on the efficacy and safety of daratumumab treatment in Hungarian relapsed/refractory multiple myeloma patients. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label Phase II study. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Monoclonal antibody Daratumumab promotes macrophage-mediated anti-myeloma phagocytic activity via engaging FC gamma receptor and activation of macrophages. [2022]

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

Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab. [2022]