Iberdomide for Multiple Myeloma

Recruiting at 63 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Active infections, Allergy to iberdomide, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 4 years

78 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares iberdomide maintenance therapy to disease monitoring for improving survival in patients who have received idecabtagene vicleucel (a type of chimeric antigen receptor T-cell \[CAR-T\] therapy) for multiple myeloma. The usual approach after treatment with idecabtagene vicleucel is to monitor the multiple myeloma without giving myeloma medications. There is currently no medication approved specifically for use after idecabtagene vicleucel treatment. Upon administration, iberdomide modifies the immune system and activates immune cells called T-cells, which could enhance the effectiveness of idecabtagene vicleucel. Iberdomide may keep multiple myeloma under control for longer than the usual approach (disease monitoring) after idecabtagene vicleucel, and may help multiple myeloma patients live longer.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you may need to switch from strong CYP3A4 inducers or inhibitors to a different medication and wait for a washout period (time without taking certain medications) before starting the trial.

What evidence supports the effectiveness of the drug Iberdomide for treating multiple myeloma?

Iberdomide, when combined with dexamethasone, has shown enhanced cancer-killing and immune-boosting effects in preclinical studies for multiple myeloma, especially in patients who have already tried many other treatments. ^{1 2 3 4 5}

Is Idecabtagene Vicleucel safe for humans?

Idecabtagene Vicleucel, a treatment for multiple myeloma, has shown some serious side effects in studies, including cytokine release syndrome (a severe immune reaction) and neurological issues in a small percentage of patients. While it has been approved for use, these potential risks mean it is important to discuss safety with your doctor. ^{6 7 8 9 10}

How is the treatment Idecabtagene Vicleucel different from other treatments for multiple myeloma?

Idecabtagene Vicleucel is a unique treatment for multiple myeloma because it is a CAR T-cell therapy, which means it uses modified immune cells to target and destroy cancer cells. This approach is different from traditional drugs and has shown significant improvements in response rates and survival for patients who have not responded to other treatments. ^{1 6 10 11 12}

Research Team

Sascha Tuchman, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for adults over 18 with multiple myeloma who've had CAR-T therapy (idecabtagene vicleucel) within the past 80-110 days. They should be in stable condition or better and haven't taken any other myeloma treatments since, except possibly short steroids for CAR-T side effects. People can't join if they're resistant to Iberdomide or have had certain recent therapies.

Inclusion Criteria

Not pregnant and not nursing

ANC must be ≥ 1,500/mm^3

All patients must be pre-registered in order to submit the required bone marrow and blood specimens

Exclusion Criteria

Known allergy to iberdomide

I have received treatment for multiple myeloma after ide-cel infusion.

Patient living outside the US

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive iberdomide orally once daily on days 1-21 of each 28-day cycle or undergo disease monitoring at monthly clinic visits.

Up to 4 years

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 years

Every 3-6 months (in-person)

Treatment Details

Interventions

• Iberdomide
• Idecabtagene Vicleucel

Trial Overview The study compares maintenance therapy using a drug called Iberdomide against just monitoring the disease after CAR-T treatment for multiple myeloma. The goal is to see if Iberdomide helps patients live longer by keeping cancer under control better than no further treatment.

Participant Groups

Group I: Group II (iberdomide) Experimental Treatment 8 Interventions

Patients receive iberdomide PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy throughout the trial, undergo collection of blood samples at screening and on study, and undergo PET/CT and/or skeletal survey x-ray, CT, or MRI at screening and then as clinically indicated.

Group II: Group 1 (monitoring) Active Control 8 Interventions

Patients undergo disease monitoring at monthly clinic visits until disease progression. Patients also undergo bone marrow aspiration and biopsy throughout the trial, undergo collection of blood samples at screening and on study, and undergo PET/CT and/or skeletal survey x-ray, CT, or MRI at screening and then as clinically indicated.

Idecabtagene Vicleucel is already approved in United States, European Union for the following indications:

Approved in United States as Abecma for:

• Relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody

Approved in European Union as Abecma for:

• Relapsed and refractory multiple myeloma who have received at least two prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

In a phase 3 trial involving 559 patients with relapsed or refractory multiple myeloma who had previously received lenalidomide, the combination of pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared to bortezomib and dexamethasone alone, with a median survival of 11.20 months versus 7.10 months.

While the combination treatment showed better efficacy, it also resulted in higher rates of serious adverse events, particularly neutropenia and infections, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Richardson, PG., Oriol, A., Beksac, M., et al.[2020]

In a phase I/II study involving 29 patients with lenalidomide and proteasome inhibitor-refractory multiple myeloma, the combination of ixazomib, pomalidomide, and dexamethasone showed a promising overall response rate of 51.7% and a median duration of response of 16.8 months.

The treatment was generally well-tolerated, with common side effects aligning with those expected from the individual drugs, suggesting that this all-oral regimen warrants further investigation in relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202). Voorhees, PM., Suman, VJ., Tuchman, SA., et al.[2022]

Bortezomib, both alone and in combination with other treatments, has demonstrated high response rates and manageable side effects in patients with relapsed or refractory multiple myeloma, indicating its efficacy and safety.

Ongoing trials of bortezomib combined with lenalidomide and dexamethasone are expected to provide important insights into its potential as a foundational treatment for advanced multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of relapsed and relapsed refractory myeloma. Kastritis, E., Mitsiades, CS., Dimopoulos, MA., et al.[2018]

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]

In a phase 2 study involving 140 patients with relapsed and refractory multiple myeloma, idecabtagene vicleucel (ide-cel) demonstrated a 73% overall response rate, with 33% achieving a complete response or better after treatment.

While ide-cel showed significant efficacy, it also resulted in high rates of toxic effects, including severe neutropenia (91%) and cytokine release syndrome (84%), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. Munshi, NC., Anderson, LD., Shah, N., et al.[2021]

Idecabtagene vicleucel (ide-cel) is a safe and effective CAR T cell therapy for relapsed/refractory multiple myeloma, showing low rates of severe side effects (6.5% cytokine release syndrome and 1.6% neurotoxicity) in a study of 62 patients with an 18.1-month follow-up.

The therapy achieved a high overall response rate of 75.8%, with 38.7% of patients reaching complete response, and the study identified specific T cell characteristics that correlate with longer-lasting responses, suggesting potential for optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Lin, Y., Raje, NS., Berdeja, JG., et al.[2023]

Idecabtagene vicleucel (ide-cel) is the first CAR T-cell therapy approved by the FDA for treating relapsed and refractory multiple myeloma, showing unprecedented results in clinical trials.

This therapy offers the potential for durable remissions and improved quality of life for patients who previously had limited treatment options, following just a single infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma. Anderson, LD.[2022]

Idecabtagene vicleucel, a CAR T-cell therapy targeting BCMA, showed a 72% overall response rate and a 28% complete response rate in 100 adult patients with relapsed/refractory multiple myeloma after a median follow-up of 10.7 months.

While the therapy demonstrated significant efficacy, serious adverse reactions were reported in 67% of patients, including cytokine release syndrome and neurologic toxicities, necessitating a Risk Evaluation and Mitigation Strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. Sharma, P., Kanapuru, B., George, B., et al.[2023]

Idecabtagene vicleucel (ide-cel) demonstrated a high overall response rate of 84% and a complete response rate of 42% in patients with relapsed/refractory multiple myeloma, based on a retrospective analysis of 159 patients who received the therapy under standard-of-care conditions.

The safety profile was consistent with previous trials, with 83% of patients experiencing cytokine release syndrome and 19% experiencing neurotoxicity, indicating that ide-cel is effective and manageable even in a population with higher comorbidities than those in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. Hansen, DK., Sidana, S., Peres, LC., et al.[2023]

In a phase 3 trial with 386 patients suffering from relapsed and refractory multiple myeloma, idecabtagene vicleucel (ide-cel) significantly improved progression-free survival (13.3 months) compared to standard treatments (4.4 months), indicating its efficacy in this challenging patient population.

The treatment with ide-cel resulted in a 71% overall response rate, including a 39% complete response rate, although it was associated with high rates of adverse events (93% grade 3 or 4), including cytokine release syndrome in 88% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. Rodriguez-Otero, P., Ailawadhi, S., Arnulf, B., et al.[2023]

Idecabtagene vicleucel (ide-cel) significantly improved overall response rates in patients with triple-class exposed relapsed and refractory multiple myeloma, showing an odds ratio of 5.30 compared to conventional care.

Patients treated with ide-cel also experienced better progression-free survival and overall survival, with hazard ratios of 0.50 and 0.37, respectively, indicating a substantial benefit over conventional treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. Shah, N., Mojebi, A., Ayers, D., et al.[2022]

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. England pubmed.ncbi.nlm.nih.gov

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. [2020]

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

A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202). [2022]

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

Management of relapsed and relapsed refractory myeloma. [2018]

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

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

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

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. [2021]

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

Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma. [2022]

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

FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. [2023]

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

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. [2023]

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

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. [2022]