Quadruple Therapy 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: CYP3A4/5 inhibitors

Disqualifiers: HIV, Hepatitis C, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and examine the effects of combining four treatments—iberdomide (a new potential drug), daratumumab, bortezomib, and dexamethasone—for individuals with newly diagnosed multiple myeloma. The goal is to assess how effectively this combination can inhibit the growth and spread of cancer cells. The trial seeks participants with active multiple myeloma who have received little to no prior treatment.

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 new potential drug.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that any additional agents not listed must be approved by the principal investigator, so it's best to discuss your current medications with the trial team.

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

Research has shown that combining iberdomide with daratumumab and dexamethasone maintains a safety profile similar to previous studies, indicating that side effects are consistent with past findings and suggesting general tolerability. Bortezomib, another component of this treatment, proves effective but can cause more serious side effects in about 76.9% of patients, a common occurrence in many cancer treatments.

Daratumumab, administered as a subcutaneous injection, has demonstrated safety with consistent results over time. Patients often transition from intravenous to subcutaneous administration without new safety concerns. Dexamethasone, used in treating multiple myeloma, has side effects, but reducing its dose does not appear to negatively impact patient outcomes.

Overall, while these treatments have known side effects, research suggests they are manageable, and the potential benefits for many patients are significant. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this quadruple therapy for multiple myeloma because it combines four different agents—bortezomib, daratumumab, dexamethasone, and iberdomide—each with a unique mechanism of action. Unlike standard treatments that often focus on just one or two approaches, this combination targets the cancer cells from multiple angles. Notably, iberdomide is a newer agent that works by modulating the immune system, potentially enhancing the overall effectiveness of treatment. This multi-faceted strategy aims to improve response rates and outcomes for patients, offering hope for more durable remissions.

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

This trial will evaluate a combination of four drugs—iberdomide, daratumumab, bortezomib, and dexamethasone—to treat multiple myeloma, a type of blood cancer. Daratumumab is a medicine that targets and destroys cancer cells. Bortezomib blocks certain proteins that cancer cells need to grow. Iberdomide may help the immune system fight cancer. Previous studies using some of these drugs together have shown that people with recurring or hard-to-treat multiple myeloma lived longer. This suggests that the combination could also be effective for newly diagnosed patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Prashant Kapoor, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with newly diagnosed multiple myeloma who haven't been treated or have had only one treatment cycle. They must have measurable disease, be in good physical condition, and have proper organ function. Pregnant or breastfeeding individuals can't join, nor can those unwilling to use contraception or those with certain medical conditions that could interfere with the trial.

Inclusion Criteria

I agree not to donate blood during the study.

Negative hepatitis B test

Willingness to provide mandatory bone marrow specimens for correlative research

Exclusion Criteria

I have no allergies to study drugs, haven't had major surgery, plasmapheresis, or investigational treatments recently.

I haven't had live vaccines recently and have no cancer history except MM, with some exceptions.

I am HIV positive or have active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive iberdomide, bortezomib, dexamethasone, and daratumumab in a 28-day cycle for 12 cycles

48 weeks

4 visits per cycle (in-person)

Maintenance

Patients receive iberdomide monotherapy in a 28-day cycle for up to 36 cycles

24 months

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Iberdomide

Trial Overview The IDEAL study is testing a combination of drugs: Iberdomide (an immunotherapy), Daratumumab (a monoclonal antibody), Bortezomib (blocks enzymes for cell growth), and Dexamethasone (chemotherapy). The goal is to find the best dose of Iberdomide and see how well these drugs work together against multiple myeloma.

How Is the Trial Designed?

Group I: Treatment (iberdomide, bortezomib, dexamethasone, daratumumab) Experimental Treatment 4 Interventions

INDUCTION PHASE: Patients receive iberdomide PO QD on days 1-21, bortezomib SC on days, 1, 8, 15, and 22, and dexamethasone PO on days 1, 8, 15, 22. Patients also receive 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. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. CYCLES 13-36 CYCLES: Patients receive iberdomide PO QD on days 1-21. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 78 patients with relapsed or refractory multiple myeloma, the combination of bortezomib, bendamustine, and prednisone showed a 69% response rate, indicating significant efficacy in treating this condition.

Patients without severe prior hematological toxicities had a median progression-free survival (PFS) of 11 months and overall survival (OS) of 50 months, while those with severe toxicities had much poorer outcomes, highlighting the importance of patient health status in treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma. Pönisch, W., Bourgeois, M., Moll, B., et al.[2021]

In a study of 16 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone resulted in a high clinical response rate of 87.5%, with 6 patients achieving near complete response.

The treatment was associated with manageable side effects, primarily gastrointestinal issues and thrombocytopenia, which were alleviated with supportive care, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. Yuan, ZG., Hou, J., Zhou, F., et al.[2015]

In two phase 2 studies involving 256 patients with relapsed or refractory multiple myeloma, adding dexamethasone to bortezomib improved treatment responses, with 18% of patients in the SUMMIT study and 33% in the CREST study showing better outcomes.

The combination therapy did not significantly increase the type or number of adverse events, indicating that dexamethasone can enhance efficacy without adding prohibitive toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Jagannath, S., Richardson, PG., Barlogie, B., et al.[2022]

In a study of 24 multiple myeloma patients treated with bortezomib and dexamethasone, 79.2% showed a positive response, with a notably higher complete remission rate in light-chain type patients (57.1%) compared to non-light-chain type patients (5.9%).

The treatment was found to be safe for patients with renal impairment, as their renal function improved during chemotherapy, and the adverse events were manageable, with most patients tolerating the side effects well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of bortezomib combined dexamethasone in 24 patients with multiple myeloma]. Li, J., Zhao, Y., Luo, SK., et al.[2015]

Bortezomib is recommended for use in both newly diagnosed and relapsed/refractory multiple myeloma patients, whether they are eligible for autologous stem cell transplantation or not, based on a systematic review of evidence.

The guidelines also emphasize the importance of monitoring and managing potential toxicities associated with bortezomib treatment, such as the risk of herpes zoster reactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in multiple myeloma: a practice guideline. Kouroukis, CT., Baldassarre, FG., Haynes, AE., et al.[2015]

In a study comparing two induction therapies for newly diagnosed multiple myeloma, the quadruplet regimen (D-VTd) showed significantly better response rates after treatment, with 90.5% achieving complete remission (CR) or stringent complete remission (sCR) compared to 68.6% in the triplet regimen (VRd).

The quadruplet regimen (D-VTd) also resulted in a higher rate of very good partial response (VGPR or better) at 93%, compared to 67.6% in the triplet regimen (VRd), although VRd was associated with a higher incidence of skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study. Byun, JM., Park, SS., Yoon, SS., et al.[2023]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

Bortezomib is the first proteasome inhibitor approved for treating multiple myeloma (MM), showing significant survival benefits as a mono-therapy and in combination with other drugs.

The neurotoxicity associated with bortezomib has been reduced through subcutaneous administration and weekly dosing, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib for the treatment of multiple myeloma. Grosicki, S., Barchnicka, A., Jurczyszyn, A., et al.[2015]

In a study of 23 patients with relapsed or refractory multiple myeloma, both low (1.0 mg/m2) and standard (1.3 mg/m2) doses of bortezomib combined with dexamethasone showed similar response rates, with 70% for the low dose and 61.5% for the standard dose, indicating that lower doses can be just as effective.

However, the standard dose of 1.3 mg/m2 was associated with more adverse effects, including serious infections and treatment-related deaths, suggesting that while it may be more effective, it also carries a higher risk of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of bortezomib at different doses in combination with dexamethasone in treatment of relapsed or refractory multiple myeloma: a comparative study]. Bao, L., Lu, XJ., Zhang, XH., et al.[2015]

In a study of 669 patients with relapsed multiple myeloma, bortezomib demonstrated significantly higher response rates and longer survival compared to high-dose dexamethasone, with complete response rates of 6% versus less than 1%.

Patients treated with bortezomib had a median time to progression of 6.22 months compared to 3.49 months for those on dexamethasone, indicating bortezomib's greater efficacy in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. Richardson, PG., Sonneveld, P., Schuster, MW., et al.[2022]

In a study of 96 relapsed/refractory multiple myeloma patients treated with the CyBorP/D regimen, 69% achieved at least a partial response, indicating strong efficacy of this treatment approach.

The regimen was generally well-tolerated, with mild and manageable toxicities, although some patients experienced new or worsening peripheral neuropathy; importantly, no second primary malignancies were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide and Bortezomib With Prednisone or Dexamethasone for the Treatment of Relapsed and Refractory Multiple Myeloma. Reece, DE., Trieu, Y., Masih-Khan, E., et al.[2018]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04975997

NCT04975997 | Open-label Study Comparing Iberdomide, ... To evaluate clinical efficacy in terms of overall survival (OS) in participants with relapsed or refractory multiple myeloma (RRMM) treated with iberdomide, ...

2. euclinicaltrials.eu euclinicaltrials.eu/ctis-public/view/2024-510800-35-00?lang=en

Clinical Trials in the European Union - EMA A clinical study that compares a treatment with Iberdomide, Daratumumab and Dexamethasone against a treatment with Daratumumab, Bortezomib, and ...

3. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT04975997

Trial ID CC-220-MM-002 | NCT04975997 - BMS Clinical Trials This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in combination with ...

4. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=19900&isClinicalTrial=True

ANZCTR - Registration To compare the efficacy of iberdomide (also known as BMS-986382), daratumumab, and dexamethasone (IberDd) to that of daratumumab, bortezomib, ...

5. bmsstudyconnect.com bmsstudyconnect.com/mx/en/clinical-trials/NCT04975997.html

Open-label Study Comparing Iberdomide, Daratumumab and ... This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5529203/

Efficacy and safety of bortezomib maintenance in patients ... Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to ...

7. myeloma.org myeloma.org/velcade-bortezomib

Velcade (Bortezomib) & Multiple Myeloma Treatment | IMF Several clinical trials have confirmed the safety and efficacy of Velcade for patients with renal (kidney) impairment. Clinical trials with Velcade have also ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118465573

Safety and Efficacy of Bortezomib (VELCADE™) in 104 ... Overall, 76.9% of the pts experienced Grade 3 & 4 adverse events. Safety profile observed is similar to past trial results with bortezomib. Conclusion: In this ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

Daratumumab, Bortezomib, Lenalidomide, and ... The subgroup analysis for type of multiple myeloma was performed with data from patients who had measurable disease in serum. Cytogenetic risk was assessed ...

10. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(19)32010-5/fulltext

Three-year Follow-up of CASTOR After 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D ...