Idecabtagene Vicleucel + Lenalidomide for Multiple Myeloma

(KarMMa-9 Trial)

Recruiting at 207 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Must be taking: Immunomodulatory drugs, Proteasome inhibitors

Disqualifiers: CNS involvement, Non-secretory MM, Infections, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: Up to approximately 50 months

618 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy, safety, and tolerability of ide-cel with lenalidomide (LEN) maintenance to that of LEN maintenance alone in adult participants with Newly Diagnosed Multiple Myeloma (NDMM) who have achieved a suboptimal response post autologous stem cell transplantation (ASCT).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not have confirmed progression since starting induction therapy and must have recovered from prior treatments, which might imply some restrictions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Idecabtagene Vicleucel + Lenalidomide for treating multiple myeloma?

Lenalidomide, one of the drugs in the treatment, has been shown to improve responses and prolong survival in multiple myeloma patients, especially when combined with other drugs like dexamethasone. Additionally, lenalidomide can enhance the body's immune response, which may help in fighting the cancer. ^{1 2 3 4 5}

Is Idecabtagene Vicleucel + Lenalidomide safe for humans?

Idecabtagene Vicleucel, used for multiple myeloma, has shown some serious side effects in clinical trials, including cytokine release syndrome (a severe immune reaction) and neurological issues in a small percentage of patients. While it has been effective for some, these potential risks should be discussed with a healthcare provider. ^{6 7 8 9 10}

What makes the treatment Idecabtagene Vicleucel unique for multiple myeloma?

Idecabtagene Vicleucel is a unique treatment for multiple myeloma because it is a CAR T-cell therapy that targets the B-cell maturation antigen, offering significant improvements in response rates and survival compared to conventional care for patients who have already tried multiple other treatments. ^{6 7 9 10 11}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Adults over 18 with newly diagnosed Multiple Myeloma who've had a stem cell transplant but didn't respond well. They should have completed specific induction therapy and be in good physical condition, without severe ongoing infections or previous gene/cell therapies.

Inclusion Criteria

I can do all or most of my daily activities despite my cancer, or I have ECOG 2 due to pain from bone lesions.

My cancer has partially or very good partially responded to treatment.

I am over 18, have new multiple myeloma, and had specific treatments without follow-up therapy, except for a short lenalidomide course.

Exclusion Criteria

Participant has history of primary immunodeficiency.

My myeloma has spread to my brain or spinal cord.

Other protocol-defined Inclusion/Exclusion criteria apply.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Idecabtagene Vicleucel with Lenalidomide maintenance or Lenalidomide maintenance alone

Up to approximately 50 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 60 months

Treatment Details

Interventions

• Cyclophosphamide
• Fludarabine
• Idecabtagene Vicleucel
• Lenalidomide

Trial Overview The trial is testing if adding idecabtagene vicleucel (ide-cel) to lenalidomide maintenance therapy is better than lenalidomide alone for Multiple Myeloma patients post-transplant with suboptimal response.

Participant Groups

Group I: Arm A Experimental Treatment 4 Interventions

Group II: Arm B Active Control 1 Intervention

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?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

2seventy bio

Industry Sponsor

Trials

3

Recruited

110+

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

Lenalidomide is a powerful treatment for multiple myeloma (MM) that works by directly causing cancer cell death, preventing cancer cells from sticking to bone marrow, and enhancing the body's immune response against tumors.

In combination with dexamethasone, lenalidomide has shown superior effectiveness in clinical trials, leading to improved patient outcomes such as longer survival and FDA approval for treating relapsed MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Hideshima, T., Raje, N., Richardson, PG., et al.[2021]

In a phase III study involving 155 multiple myeloma patients, bortezomib and lenalidomide treatments showed similar effectiveness, with 15% and 18% of patients achieving a very good partial response (VGPR) respectively, indicating comparable efficacy.

Both treatment regimens resulted in similar median progression-free survival (PFS) of 16.3 months for bortezomib and 18.6 months for lenalidomide, along with comparable two-year overall survival rates of 75% and 74%, confirming their safety and effectiveness in managing multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. Montefusco, V., Corso, A., Galli, M., et al.[2020]

In an early phase clinical trial involving patients with relapsed multiple myeloma, lenalidomide was shown to enhance immune responses to the pneumococcal vaccine, particularly when both vaccinations were given while on lenalidomide.

Patients who responded clinically to myeloma treatment exhibited increased tumor-specific immune responses, indicating that lenalidomide may not only boost vaccine efficacy but also enhance the body's ability to fight cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Noonan, K., Rudraraju, L., Ferguson, A., et al.[2021]

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]

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 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, 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]

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]

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]

References

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

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. [2020]

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

Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. [2021]

4. 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]

5. 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]

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

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

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

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

10. England pubmed.ncbi.nlm.nih.gov

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

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

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