Elotuzumab + Daratumumab + Iberdomide + Dexamethasone for Multiple Myeloma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: NSAIDs, Immunosuppressants, others

Disqualifiers: HIV, Hepatitis, Cardiovascular disease, 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: Up to 36 months

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to determine their safety and effectiveness in treating multiple myeloma, a type of blood cancer that has returned after a period of improvement. The trial tests a mix of drugs, including iberdomide, which boosts the immune system, and two monoclonal antibodies, daratumumab and elotuzumab, that target and help destroy cancer cells. Dexamethasone is included to manage inflammation and side effects. Suitable candidates for this trial have multiple myeloma that has recurred after three or fewer treatments, including certain previous drugs, and have not been treated with iberdomide before. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have taken certain medications like strong CYP3A4/5 inhibitors or inducers, and some immunomodulating or immunosuppressive therapies recently. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

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

Research shows that the combination of treatments, including iberdomide, daratumumab, elotuzumab, and dexamethasone, is generally well-tolerated by patients with multiple myeloma. Studies have found that the safety profile of iberdomide with daratumumab and dexamethasone aligns with observations from other research, indicating that serious side effects are uncommon.

Other research on similar drug combinations for patients whose multiple myeloma has returned or not responded to treatment showed positive results without severe side effects. This suggests that patients generally handled the treatment well, although mild to moderate side effects might occur.

These findings offer hope that the treatment can be safe for most patients. However, individual experiences may vary, so discussing any concerns with a healthcare provider before joining a clinical trial is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for multiple myeloma because it brings together three powerful drugs: daratumumab, elotuzumab, and iberdomide. Unlike traditional treatments that often target the cancer cells directly, this combination works synergistically, each drug enhancing the other's effects to boost the immune system's ability to fight the cancer. For example, daratumumab targets a specific protein on myeloma cells, while elotuzumab activates immune cells to attack the cancer, and iberdomide modulates the immune response. This multi-faceted approach could potentially offer a more effective treatment option with the possibility of improved outcomes for patients.

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

Research has shown that a combination of the drugs elotuzumab, daratumumab, iberdomide, and dexamethasone, which participants in this trial will receive, may effectively treat relapsed multiple myeloma. In earlier studies with similar drug combinations, patients demonstrated a significant response. Specifically, one study reported that 52.6% of patients responded to the treatment, with the disease not worsening for about 6.6 months on average, and patients living for about 17 months overall. Elotuzumab and daratumumab specifically target and help destroy cancer cells, while iberdomide may enhance the immune system's ability to fight cancer. Together, these treatments aim to slow the disease and improve patient outcomes. ^{1 6 7 8 9}

Who Is on the Research Team?

Moritz Binder, MD, MPH

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that has relapsed. Participants should have previously responded to treatment but now show signs of the disease returning. Specific eligibility criteria are not provided, so interested individuals should inquire further to determine if they meet the necessary requirements for participation.

Inclusion Criteria

Absolute neutrophil count (ANC) ≥ 1000/m^3

Provide written informed consent

My cancer can be measured by tests.

Exclusion Criteria

I have recently taken certain medications.

Known allergy to study medications or excipients

Co-morbidities interfering with trial participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive iberdomide, daratumumab, elotuzumab, and dexamethasone in 28-day cycles for up to 36 cycles

Up to 36 months

Weekly visits during initial cycles, then bi-weekly or monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 3 years

Follow-up at 7 days, 30 days, then every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Dexamethasone
• Elotuzumab
• Iberdomide

Trial Overview The trial is testing a combination therapy using iberdomide, daratumumab, elotuzumab, and dexamethasone to see how safe it is and what dose works best against relapsed multiple myeloma. It's in phases I/II, which means early stages of evaluating effectiveness and safety.

How Is the Trial Designed?

Group I: Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone) Experimental Treatment 11 Interventions

Patients receive iberdomide PO QD on days 1-21 of each cycle, daratumumab SC on days 1, 8, 15, 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive elotuzumab IV on days 1, 8, 15, and 22 of cycles 1 and 2, and on day 1 of subsequent cycles and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12 or at the discretion of the treating physician. Cycles repeat every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy during screening, on study and optionally at disease progression and CT, bone scan, MRI or PET/CT during screening, on study or at the discretion of the treating physician and EOT. Patients may undergo chest x-ray during screening.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06785415

NCT06785415 | Elotuzumab, Daratumumab, Iberdomide, ... Giving iberdomide in combination with daratumumab, elotuzumab, and dexamethasone may be safe, tolerable and/or effective in patients with relapsed multiple ...

2. esmoopen.com esmoopen.com/article/S2059-7029(24)01854-4/fulltext

Outcomes and prognostic indicators in daratumumab ... The overall response rate was 52.6%, with a median PFS and OS of 6.6 and 17.0 months, respectively. The International Staging System (ISS) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12102281/

Real world outcomes with elotuzumab-based therapies for ... At 2 years 38.8% and 53.7% of patients had ongoing sustained response for EPd and ERd, respectively. The median PFS for patients treated with ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20579189

A Study of Elotuzumab, Daratumumab, Iberdomide, and ... The purpose of this study is to assess the maximum tolerated dose (MTD) of the combination of iberdomide, daratumumab, elotuzumab, and ...

5. trialx.com trialx.com/clinical-trials/listings/306028/elotuzumab-daratumumab-iberdomide-and-dexamethasone-for-the-treatment-of-relapsed-multiple-myeloma/

Elotuzumab, Daratumumab, Iberdomide, and ... This phase I/II trial tests the safety, side effects, and best dose of iberdomide and how well it works in combination with daratumumab, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39449301/

The Real-World Outcomes of Relapsed/Refractory Multiple ... Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00280-3/fulltext

Safety and efficacy of a dexamethasone-sparing regimen ... Patients with frailty and newly diagnosed multiple myeloma have worse outcomes due to higher rates of adverse events (AEs) and treatment discontinuation.

8. news.bms.com news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Phase-3-EXCALIBER-RRMM-Study-Evaluating-Iberdomide-in-Combination-with-Standard-Therapies-Demonstrated-a-Significant-Improvement-in-Minimal-Residual-Disease-Negativity-Rates-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx

Bristol Myers Squibb Announces Phase 3 EXCALIBER ... The safety profile of iberdomide in combination with daratumumab and dexamethasone in this study is generally consistent with previous studies.

9. onclive.com onclive.com/view/iberdomide-daratumumab-dexamethasone-is-effective-in-newly-diagnosed-multiple-myeloma

Iberdomide/Daratumumab/Dexamethasone Is Effective in ... The iberdomide-daratumumab-dexamethasone regimen achieved a 93.1% overall response rate in frail, transplant-ineligible multiple myeloma ...