Iberdomide Combo for Multiple Myeloma

(COMMANDER Trial)

Recruiting at6 trial locations

Overseen by Luciano Costa, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Amyloidosis, Hepatitis B, Heart failure, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Similar to the paradigm established in other hematologic malignancies that are considered curable, the achievement of MRD(-) status is necessary for long term disease control in MM. The fact that the majority of patients remain MRD (+) after induction therapy and AHCT points to the opportunity to deploy novel agents with complementary mechanism of action and favorable toxicity profile to reach and maintain MRD (-) status. Given its favorable toxicity profile, the convenience of oral administration, and compelling single agent activity even in heavily pretreated MM, iberdomide is likely amenable to long term therapy in patients with high-risk of relapse/progression identified by the persistence of MRD(+). The investigators intend to develop combination(s) of iberdomide with other agents with complementary mechanism of action in the consolidation setting post AHCT in order to achieve and sustain MRD (-).

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use strong inhibitors or inducers of certain enzymes (CYP3A4, P-gp, or BCRP) or specific drugs with a narrow safety margin. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination including Iberdomide for treating multiple myeloma?

Research shows that Iberdomide, when combined with dexamethasone, has shown promising results in patients with heavily pretreated relapsed or refractory multiple myeloma. Iberdomide is a new type of drug that works well with other treatments like proteasome inhibitors and CD38 monoclonal antibodies, which are part of the combination being studied. ^{1 2 3 4 5}

Is the Iberdomide combination treatment generally safe for humans?

Iberdomide, when combined with dexamethasone, has been evaluated for safety in patients with multiple myeloma, showing potential for use with other drugs like proteasome inhibitors and CD38 monoclonal antibodies. While specific safety data is not detailed, the focus on its development suggests it is considered safe enough for clinical trials. ^{1 2 3 4 6}

What makes the drug iberdomide unique for treating multiple myeloma?

Iberdomide is a new type of drug that works by targeting specific proteins called ikaros and aiolos, which makes it more precise in its action compared to older treatments. It also has enhanced effects in killing cancer cells and boosting the immune system, especially when used with other drugs like dexamethasone. ^{1 2 3 4 7}

Research Team

Luciano Costa, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

Adults diagnosed with multiple myeloma who've had 1-2 prior treatments including an immunomodulatory agent and a proteasome inhibitor, and have undergone autologous hematopoietic cell transplantation (AHCT) within the past 100-180 days. Participants must show minimal residual disease, be in partial response or better post-AHCT, and have adequate organ function. Pregnant women, those with certain other medical conditions or infections, or previous negative reactions to specific drugs are excluded.

Inclusion Criteria

Written informed consent in accordance with federal, local, and institutional guidelines

I am older than 18.

I had a stem cell transplant 100-180 days before starting the treatment in this study.

Exclusion Criteria

I am allergic to Captisol®, a substance used in some cancer drugs.

I have had a stroke before or a TIA in the last year.

My multiple myeloma has affected my brain or spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination regimens of Iberdomide with other agents to achieve and sustain MRD(-) status

6 months

Weekly visits for drug administration

Consolidation

Continuation of treatment to maintain MRD(-) status post AHCT

6 months

Bi-weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Carfilzomib (Proteasome Inhibitor)
• Daratumumab (Monoclonal Antibody)
• Dexamethasone (Corticosteroid)
• Iberdomide (Immunomodulatory Agent)

Trial Overview The trial is testing combinations of the oral drug Iberdomide with Daratumumab, Dexamethasone, and Carfilzomib for multiple myeloma patients post-AHCT. The goal is to achieve and maintain undetectable levels of cancer cells (MRD-negative status), which could lead to long-term disease control.

Participant Groups

Group I: Iberdomide, Daratumumab and Dexamethasone (Regimen A) Experimental Treatment 3 Interventions

Iberdomide dosed according to cohort assignment days 1-21. Dexamethasone 40 mg oral or intravenously (20 mg for participants 70 or older) on days 1,8,15 and 22 Darartumumab and hyalurnonidase-fihj 1,800mg/30,000 units subcutaneously on days 1,8,15,22 (cycles 1,2) or on days 1,15 (cycles 3-6)

Group II: Iberdomide, Carfilzomib, Daratumumab and Dexamethasone (Regimen B) Experimental Treatment 4 Interventions

Iberdomide dosed according to cohort assignment days 1-21. Dexamethasone 40 mg oral or intravenously (20 mg for participants 70 or older) on days 1,8,15 and 22 Darartumumab and hyalurnonidase-fihj 1,800mg/30,000 units subcutaneously on days 1,8,15,22 (cycles 1,2) or on days 1,15 (cycles 3-6) Carfilzomib dosed intravenously dosed according to cohort assignment on days 1, 8, 15 (Consistent with standard practice, the very first dose of carfilzomib (cycle 1 day 1) must be 20 mg/m\^2).

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

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

coMMit, Myeloma Trials, Innovated

Collaborator

Trials

2

Recruited

380+

Findings from Research

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]

Recent advancements in anti-myeloma treatments, including thalidomide, lenalidomide, and bortezomib, have shown significant clinical responses, especially in patients who do not respond to traditional chemotherapy.

The review highlights the ongoing development of various novel therapeutic classes, such as second-generation proteasome inhibitors and HDAC inhibitors, which are currently in clinical trials or advanced preclinical stages, indicating a promising expansion of treatment options for myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. Mitsiades, CS., Hayden, PJ., Anderson, KC., et al.[2023]

Cereblon-targeting immunomodulatory agents like lenalidomide and pomalidomide are crucial in treating Multiple Myeloma due to their ability to enhance anti-tumor effects and work well with other therapies.

Next-generation cereblon E3 ligase modulators, such as iberdomide and CC-92480, are being developed to improve treatment outcomes, highlighting the importance of understanding drug mechanisms and patient-specific factors in creating effective combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing next generation immunomodulatory drugs and their combinations in multiple myeloma. Thakurta, A., Pierceall, WE., Amatangelo, MD., et al.[2021]

Multiple myeloma remains an incurable disease with increasing incidence, and while current treatments using proteasome inhibitors and immunomodulatory drugs have improved outcomes, many patients still experience relapses and resistance.

Iberdomide, a new drug with high specificity for the Ikaros and Aiolos proteins, represents a promising direction in developing more targeted therapies for multiple myeloma, potentially improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. Zhang, Z., Liu, X., Zhao, L., et al.[2022]

Recent advancements in multiple myeloma treatment, including proteasome inhibitors and immunomodulatory drugs, have significantly improved patient outcomes, but drug resistance remains a challenge.

New therapies such as venetoclax, selinexor, iberdomide, isatuximab, and CAR T-cell therapy show promising results in overcoming resistance and improving treatment efficacy for patients with refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multiple myeloma: a focus on drugs under development]. Sunami, K.[2020]

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]

The three-drug combination of bendamustine, prednisone, and bortezomib (BPV) showed a high overall response rate of 78.8% in elderly patients with multiple myeloma, indicating its efficacy as a first-line treatment.

In patients with renal impairment, BPV not only provided a significant clinical benefit but also led to complete recovery of renal function in six out of eleven patients, highlighting its potential for treating this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line therapy with bendamustine/prednisone/bortezomib-A GMMG trial for non-transplant eligible symptomatic multiple myeloma patients. Knauf, W., Dingeldein, G., Schlag, R., et al.[2021]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. [2023]

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

Developing next generation immunomodulatory drugs and their combinations in multiple myeloma. [2021]

4. France pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Multiple myeloma: a focus on drugs under development]. [2020]

6. 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]

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

First-line therapy with bendamustine/prednisone/bortezomib-A GMMG trial for non-transplant eligible symptomatic multiple myeloma patients. [2021]