Iberdomide Combo for Multiple Myeloma

(COMMANDER Trial)

Recruiting at 6 trial locations

Overseen By Margaret A Thomas, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Alabama at Birmingham

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Amyloidosis, Hepatitis B, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve long-term control of multiple myeloma by testing combinations of the drug iberdomide with other treatments. The goal is to enhance the effectiveness of post-transplant therapies for patients whose cancer shows signs of returning. Participants should have undergone a stem cell transplant and still exhibit signs of the disease, despite previous treatments. This trial is particularly suited for those at high risk of relapse and seeking new treatment options. As a Phase 1/Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to explore new treatment avenues.

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.

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

Research has shown that iberdomide is promising in terms of safety for patients with multiple myeloma. Previous patients found iberdomide to be well-tolerated, even when combined with other drugs like carfilzomib, daratumumab, and dexamethasone. In these studies, patients experienced manageable side effects, and the treatment was generally considered safe.

For those considering joining a clinical trial with iberdomide, it's important to know that the drug has been tested in several studies, often in combination with other medications. These combination treatments aim to be more effective while keeping side effects mild and similar to those of other multiple myeloma treatments.

In summary, iberdomide, whether used alone or with other drugs, has shown a good safety record in studies so far. This makes it a promising option for long-term treatment, especially for patients at high risk of relapse. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for multiple myeloma, like lenalidomide and bortezomib, aim to block cancer cell growth. But Iberdomide is different because it targets a protein called cereblon, which helps break down proteins that cancer cells need to survive. Researchers are excited about Iberdomide because it might work in patients who no longer respond to other treatments. Plus, when combined with drugs like carfilzomib, daratumumab, and dexamethasone, Iberdomide could enhance their effectiveness, offering new hope for better outcomes.

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

Research has shown that iberdomide, when combined with other drugs like daratumumab and dexamethasone, can effectively treat multiple myeloma. In this trial, some participants will receive this combination, which has significantly reduced cancer, even in patients who cannot undergo a transplant. Iberdomide works by directly killing cancer cells and aiding the immune system in fighting the disease. Another group in this trial will receive an additional drug, carfilzomib, in their treatment regimen. Studies suggest that adding carfilzomib helps patients live longer without disease progression. Overall, these drug combinations show promise in controlling multiple myeloma and improving patient outcomes. ^{1 3 4 6 7}

Who Is on the Research Team?

Luciano Costa, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Iberdomide

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.

How Is the Trial Designed?

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+

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+

coMMit Myeloma Trials

Collaborator

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09012

Iberdomide, Daratumumab, Carfilzomib, and ... Iberdomide may be able to suppress multiple myeloma by directly killing cancer cells and also by stimulating the immune system. Daratumumab is in a class of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10368773/

Final analysis of carfilzomib, dexamethasone, and ... The final analysis of CANDOR confirmed a PFS benefit and showed a trend in OS favoring KdD vs Kd. Results reinforce KdD as a standard of care for RRMM, ...

4. 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 ...

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

Iberdomide/Daratumumab/Dexamethasone Is Effective in ... Iberdomide plus daratumumab and dexamethasone yielded deep responses and had a manageable safety profile in transplant-ineligible multiple ...

6. clinicaltrials.eu clinicaltrials.eu/inn/iberdomide/

Iberdomide – Application in Therapy and Current Clinical ... Iberdomide is currently being studied in several clinical trials to evaluate its safety and effectiveness. Some key studies include: A phase 2 study comparing ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05199311

NCT05199311 | Carfilzomib, Iberdomide (CC-220) and ... This is a multi-institution, open label, phase I/II study of Iberdomide, Carfilzomib, and dexamethasone (KID) in patients with newly diagnosed transplant ...