Radioimmunotherapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Anti-CD38 antibodies

Must not be taking: Chemotherapy, Radiation, Biologics

Disqualifiers: Asthma, COPD, HIV, others

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

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

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose and side effects of a new combination treatment for multiple myeloma, a type of blood cancer that has returned or does not respond to standard treatments. The treatment combines a monoclonal antibody, a protein designed to target cancer cells, with a radioactive element to deliver therapy directly to the cancer cells. This approach, known as radioimmunotherapy, may suit patients who have tried at least two other treatments without success. The trial seeks to determine if this combination can effectively kill more cancer cells. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot receive concurrent chemotherapy, radiation, or biologic treatments for cancer. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that daratumumab, a key component of this trial's treatment, is generally well-tolerated by patients with multiple myeloma. Common side effects, such as upper respiratory tract infections, are manageable. The FDA has approved daratumumab for treating multiple myeloma, confirming its known safety profile.

The trial also includes actinium Ac 225-DOTA-daratumumab and indium In 111-DOTA-daratumumab, new forms of radioimmunotherapy. As this is an early-stage trial, detailed information about their safety in humans remains limited. The goal is to target cancer cells more precisely, potentially reducing harm to healthy cells. Initial studies focus on determining the optimal dose and closely monitoring any side effects.

The current priority is to ensure these new treatments are safe for further testing, which is why researchers administer and monitor them carefully during this trial phase. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which often involve chemotherapy or proteasome inhibitors, the treatment using Actinium Ac 225-DOTA-Daratumumab and Indium In 111-DOTA-Daratumumab is unique because it combines radioimmunotherapy with a monoclonal antibody. This innovative approach allows the targeted delivery of radiation directly to the cancer cells, minimizing damage to healthy tissues. Researchers are excited about this treatment because it harnesses the precision of radioisotopes to enhance the efficacy of daratumumab, potentially leading to more effective and less toxic treatment options for patients with multiple myeloma.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research shows that daratumumab, a type of antibody, effectively treats multiple myeloma, a kind of blood cancer. It has helped about 30% of patients whose cancer returned or didn't respond to earlier treatments. In this trial, participants will receive daratumumab followed by Actinium Ac 225-DOTA-daratumumab and Indium In 111-DOTA-daratumumab. Actinium Ac 225-DOTA-daratumumab combines daratumumab with a radioactive element and demonstrated much stronger cancer-fighting effects in mice, suggesting it might better find and destroy cancer cells. Indium In 111-DOTA-daratumumab also uses a radioactive tracer to deliver treatment directly to cancer cells. This targeted method aims to improve treatment by focusing directly on the cancer cells. ^{1 4 6 7 8}

Who Is on the Research Team?

Scott R Goldsmith

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with multiple myeloma that's resistant to treatment or has returned. They must have tried at least two prior therapies, including a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 monoclonal antibody. Participants need good organ function and performance status, not be pregnant or breastfeeding, use effective birth control if applicable, and can't have other active cancers or severe lung/heart conditions.

Inclusion Criteria

Your absolute neutrophil count is at least 1,000 per cubic millimeter.

I am a man and will use protection if I have sex with a woman who can have children.

My multiple myeloma cells show CD38 expression.

Exclusion Criteria

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study

I have not had a heart attack in the last 12 months.

You have a serious abnormality in your heart's electrical activity as shown by an ECG test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab IV over 45 minutes, followed by 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab IV over 20-30 minutes

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Weekly for 8 weeks, every 2 weeks for 4 weeks, every 4 weeks for 16 weeks, then periodically up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Actinium Ac 225-DOTA-Daratumumab
• Daratumumab
• Indium In 111-DOTA-Daratumumab

Trial Overview The trial tests the safety and optimal dose of a new therapy combining three agents: Actinium Ac 225-DOTA-daratumumab (radioimmunotherapy), Daratumumab (monoclonal antibody), and Indium In 111-DOTA-daratumumab (another radioimmunotherapy). This combination aims to target cancer cells more effectively in those with refractory or recurrent multiple myeloma.

How Is the Trial Designed?

Group I: Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab) Experimental Treatment 3 Interventions

Patients receive daratumumab IV over 45 minutes. Two hours later, patients receive 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab IV over 20-30 minutes.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a preclinical study of multiple myeloma, the α-emitter 225Ac-DOTA-daratumumab showed superior efficacy compared to the β-emitter 177Lu-DOTA-daratumumab, significantly extending survival and delaying tumor growth at lower doses.

While both therapies had potential for toxicity at higher doses, 225Ac-DOTA-daratumumab achieved better outcomes with less whole-body toxicity, indicating it may be a more effective targeted therapy for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of CD38-Targeted α- Versus β-Radionuclide Therapy of Disseminated Multiple Myeloma in an Animal Model. Minnix, M., Adhikarla, V., Caserta, E., et al.[2022]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

Daratumumab administered subcutaneously (SC) significantly reduces the time healthcare providers spend on drug preparation and administration compared to intravenous (IV) administration, with a 63.8% reduction in active HCP time for first treatments.

The SC formulation also drastically decreases patient chair time by 97%, making the treatment process more efficient and potentially increasing patient access to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Time and Motion Survey Regarding Subcutaneous versus Intravenous Administration of Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma. Slavcev, M., Spinelli, A., Absalon, E., et al.[2022]

Daratumumab received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

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]

Daratumumab, when radiolabeled with the alpha-emitter 225Ac, effectively kills CD38-positive tumor cells in vitro while maintaining its original immune functions, suggesting enhanced therapeutic potential for multiple myeloma.

In mouse models, 225Ac-daratumumab showed significantly increased antitumor effects compared to the non-radiolabeled version, with prolonged tumor retention and no significant side effects observed over a 50-day treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab-225Actinium conjugate demonstrates greatly enhanced antitumor activity against experimental multiple myeloma tumors. Dawicki, W., Allen, KJH., Jiao, R., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05363111

Study Details | NCT05363111 | Radioimmunotherapy ... This phase I trial tests the safety, side effects, and best dose of actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-daratumumab) in combination with ...

2. withpower.com withpower.com/trial/phase-1-refractory-plasma-cell-myeloma-5-2022-a7b3b

Radioimmunotherapy for Multiple Myeloma In mouse models, 225Ac-daratumumab showed significantly increased antitumor effects compared to the non-radiolabeled version, with prolonged tumor retention and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31413916/

Daratumumab- 225 Actinium conjugate demonstrates ... Daratumumab-225Actinium conjugate demonstrates greatly enhanced antitumor activity against experimental multiple myeloma tumors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05363111?intr=%22Daratumumab%22&viewType=Table&rank=1

Radioimmunotherapy (111Indium/225Actinium-DOTA- ... This phase I trial tests the safety, side effects, and best dose of actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-daratumumab) in combination with ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/actinium-ac-225-dota-daratumumab

Clinical Trials Using Actinium Ac 225-DOTA-Daratumumab Review the clinical trials studying actinium ac 225-dota-daratumumab on this list and use the filters to refine the results by age and location.

6. myeloma.org myeloma.org/sparkcures/trial/1282/NCT05363111

Radioimmunotherapy This phase I trial tests the safety, side effects, and best dose of actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-daratumumab) in combination with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11562018/

Mathematical Modeling Unveils Optimization Strategies for ... Clinical trials have shown favorable safety profile of daratumumab (4). However, its action results in highly heterogeneous outcomes, including frequent cancer ...

8. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/actinium-ac-225-dota-daratumumab

Definition of Actinium Ac 225-DOTA-Daratumumab Actinium Ac 225-DOTA-Daratumumab. A radioimmunoconjugate containing daratumumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody directed against ...