Iberdomide + Elotuzumab + Dexamethasone for Multiple Myeloma

(CC-220 Trial)

Recruiting in New York (>99 mi)

Overseen By Donna Catamero, MSH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Plasmacytoma, Plasma cell leukemia, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm, open-label study evaluating the safety, tolerability and efficacy of Iberdomide (CC-220) in combination with Elotuzumab and Dexamethasone in patients with RRMM. The researchers hypothesize that the combination of Iberdomide and Elotuzumab will synergize to promote myeloma cell death, resulting in an overall response rate of at least 53%, with an acceptable safety profile. Patients will be enrolled in a 3+3 dose escalation cohort to evaluate the safety of this combination and to establish the MTD (maximum tolerated dose). The MTD will be the dose for the patients enrolled in dose expansion cohort. A total maximum of 37 patients will be recruited: maximum 18 patients will be recruited in the dose escalation phase, followed by an additional 19 patients in the dose expansion cohort for a total of 25 patients treated at the MTD.

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

The trial requires that you stop any anti-myeloma drug therapy within 14 days before starting the study treatment and any experimental drug therapy within 28 days. Additionally, you must not have taken melphalan within 4 weeks or corticosteroids (other than Dexamethasone) within 3 weeks before the first dose of the study drug.

What data supports the effectiveness of the drug combination Iberdomide, Elotuzumab, and Dexamethasone for treating multiple myeloma?

Research shows that Iberdomide combined with Dexamethasone has shown promising results in treating heavily pretreated multiple myeloma, and Elotuzumab combined with other drugs like Lenalidomide and Dexamethasone has been effective in improving survival and response rates in similar patient groups. ^{1 2 3 4 5}

Is the combination of Iberdomide, Elotuzumab, and Dexamethasone safe for humans?

Iberdomide combined with dexamethasone has been studied for safety in patients with multiple myeloma, showing it can be used safely in heavily pretreated patients. Elotuzumab, when combined with lenalidomide and dexamethasone, has been approved by the FDA for multiple myeloma, but it comes with warnings for infusion reactions, infections, and other serious side effects. Overall, these components have been evaluated for safety in humans, but they do have potential side effects that need to be managed. ^{1 2 6 7 8}

What makes the drug combination of Iberdomide, Elotuzumab, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because Iberdomide is a new type of drug that enhances the body's immune response and works well with Dexamethasone, while Elotuzumab targets a specific protein on myeloma cells, making the treatment potentially more effective for patients who have already tried other therapies. ^{1 2 4 8 9}

Research Team

Samir Parekh

Principal Investigator

Icahn school of medicine

Cesar Rodriguez, MD

Principal Investigator

Icahn School of Medicine

Eligibility Criteria

Adults with relapsed/refractory multiple myeloma who have had 1-3 prior treatments including specific therapies (IMiD, proteasome inhibitor, anti-CD38 agent) can join. They must not be pregnant or breastfeeding and agree to use contraception. Excluded are those with certain other medical conditions, recent surgeries, active infections requiring long-term treatment, or previous Iberdomide/Elotuzumab use.

Inclusion Criteria

You have more than 200 milligrams of M-protein in your urine in a 24-hour sample.

Before joining the study, you must have a disease that can be measured or seen on tests.

You have high levels of M-protein in your blood.

Exclusion Criteria

I haven't had major heart surgery in the last 8 weeks or any other major surgery in the last 4 weeks.

You had a very bad allergic reaction to a medication called IMiD in the past.

Your liver enzymes are more than three times the normal level.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding

Open-label, sequential allocation, dose-finding evaluation of Iberdomide in combination with Elotuzumab and Dexamethasone to determine the maximum tolerated dose

28 days

Dose-Expansion

Open-label, single-arm dose expansion cohort to verify safety and tolerability and examine anti-myeloma activity at the maximum tolerated dose

up to 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexamethasone
• Elotuzumab
• Iberdomide

Trial Overview The trial tests a combination of Iberdomide (CC-220), Elotuzumab, and Dexamethasone in patients whose multiple myeloma has returned after treatment. It's an open-label study where everyone gets the same drugs but at different doses to find the highest dose that's safe (MTD). Up to 37 people will participate.

Participant Groups

Group I: Iberdomide, Elotuzumab and Dexamethasone Experimental Treatment 3 Interventions

Dose-Finding: Patients will be enrolled in a 3+3 dose escalation cohort. Dose-Expansion: additionally enrolled patients at the recommended maximum tolerated dose of Iberdomide as was determined in Part 1 (Dose-Finding Phase).

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a study of 117 patients with relapsed or refractory multiple myeloma, those treated with elotuzumab plus pomalidomide and dexamethasone experienced a median progression-free survival of 10.3 months, compared to 4.7 months for those receiving pomalidomide and dexamethasone alone, indicating a significant improvement in treatment efficacy.

The overall response rate was also higher in the elotuzumab group at 53% versus 26% in the control group, with fewer severe adverse events like neutropenia and anemia, suggesting that elotuzumab may enhance treatment outcomes while maintaining a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2019]

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]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

In the phase III ELOQUENT-2 trial involving adults with relapsed multiple myeloma, elotuzumab combined with lenalidomide and dexamethasone significantly improved progression-free survival and overall response rates compared to the standard treatment alone.

The addition of elotuzumab did not negatively affect health-related quality of life and had a manageable safety profile, with the most common serious side effects being blood-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Lamb, YN.[2019]

Both high-dose and low-dose dexamethasone combined with bortezomib and thalidomide significantly improved the overall remission rate in 96 patients with multiple myeloma compared to a placebo, with no significant difference in efficacy between the two dexamethasone doses.

The low-dose dexamethasone regimen resulted in fewer adverse reactions, such as fatigue and peripheral neuropathy, indicating better safety while maintaining similar therapeutic benefits as the high-dose regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy and Safety of Different Doses of Dexamethasone Combined with Bortezomib and Thalidomide for Treating Patients with Multiple Myeloma]. Li, CS., Ji, Y., Zhang, WP., et al.[2018]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

Elotuzumab, when combined with lenalidomide and dexamethasone, significantly improves progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma, with a median PFS of 19.4 months compared to 14.9 months for the standard treatment.

The treatment showed a higher overall response rate (ORR) of 75.8% versus 65.5% for the standard therapy, although serious adverse reactions were more common in the elotuzumab group (65% vs. 57%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. Gormley, NJ., Ko, CW., Deisseroth, A., et al.[2018]

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]

In a phase 1/2 trial involving 65 patients with newly diagnosed multiple myeloma, the combination of oral ixazomib, lenalidomide, and dexamethasone was found to be generally well tolerated, with a maximum tolerated dose of ixazomib established at 2.97 mg/m².

The treatment resulted in a very good partial response or better in 58% of patients, indicating significant efficacy and supporting further phase 3 trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Kumar, SK., Berdeja, JG., Niesvizky, R., et al.[2019]

References

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

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. [2019]

2. England 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. [2022]

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

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy and Safety of Different Doses of Dexamethasone Combined with Bortezomib and Thalidomide for Treating Patients with Multiple Myeloma]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

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

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. [2018]

8. Greece 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. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. [2019]