Ide-cel + Lenalidomide for Multiple Myeloma

(KarMMa-9 Trial)

Recruiting at 114 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.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 60 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 information 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, 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 Lenalidomide for treating multiple myeloma?

Lenalidomide, when combined with dexamethasone, has been shown to improve response rates and extend survival in patients with relapsed or refractory multiple myeloma, as demonstrated in pivotal phase III trials. This combination is effective in improving overall survival and progression-free survival compared to dexamethasone alone. ^{1 2 3 4 5}

Is the Ide-cel + Lenalidomide treatment safe for humans?

Research shows that Idecabtagene vicleucel (ide-cel) is generally safe for humans, with low rates of serious side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (damage to the nervous system). ^{6 7 8 9 10}

What makes the drug Ide-cel + Lenalidomide unique for treating multiple myeloma?

Idecabtagene Vicleucel (Ide-cel) is a type of CAR T-cell therapy, which is a personalized treatment that uses a patient's own immune cells to target and destroy cancer cells. This approach is different from traditional drugs like lenalidomide, which modulate the immune system more broadly. ^{3 5 11 12 13}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with newly diagnosed Multiple Myeloma who haven't responded well to a stem cell transplant. Participants should be in good health otherwise and not have any other major illnesses or conditions that could interfere with the study.

Inclusion Criteria

Participant must have documented response of PR or VGPR at time of consent.

I have recovered from previous treatment side effects, except for hair loss and mild nerve pain.

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

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply.

Participant has history of primary immunodeficiency.

My multiple myeloma does not produce detectable levels of M protein.

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 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Treatment Details

Interventions

• Cyclophosphamide
• Fludarabine
• Idecabtagene Vicleucel
• Lenalidomide

Trial Overview The study is testing if adding idecabtagene vicleucel (ide-cel) to lenalidomide maintenance therapy works better than lenalidomide alone after a suboptimal response to stem cell transplantation in treating Multiple Myeloma.

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

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 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]

Lenalidomide, when combined with dexamethasone, significantly improves response rates and survival in patients with relapsed/refractory multiple myeloma, showing a response rate of 60% compared to 20% with placebo in Phase III trials.

While lenalidomide is effective, it is associated with common adverse events such as hematologic toxicity and venous thromboembolism, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment strategies with lenalidomide in multiple myeloma and future perspectives. Larocca, A., Cavallo, F., Mina, R., et al.[2018]

In a study of 858 patients with relapsed/refractory multiple myeloma treated with lenalidomide and dexamethasone, the overall response rate was 46.3%, indicating significant efficacy across various treatment lines.

Patients with high-risk cytogenetic aberrations had a lower response rate (26.4%) and shorter overall survival (15.7 months) compared to the overall cohort, highlighting the need for tailored treatment approaches in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide and dexamethasone in treatment of patients with relapsed and refractory multiple myeloma - analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies. Maisnar, V., Stefanikova, Z., Spicka, I., et al.[2019]

Lenalidomide, when combined with dexamethasone (Len/Dex), significantly improves overall survival in patients with relapsed or refractory multiple myeloma compared to dexamethasone alone, as shown in pivotal phase III trials.

Lenalidomide has a manageable safety profile with minimal neurotoxicity, making it suitable for long-term use, and is also effective as an induction therapy for newly diagnosed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How lenalidomide is changing the treatment of patients with multiple myeloma. Dimopoulos, MA., Terpos, E., Niesvizky, R.[2013]

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]

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]

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) 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]

Idecabtagene vicleucel (ide-cel) therapy significantly improves survival in patients with relapsed/refractory multiple myeloma, providing an additional 2.64 life-years and 2.31 quality-adjusted life-years (QALYs) compared to conventional care.

The cost-effectiveness analysis showed that ide-cel has an incremental cost-effectiveness ratio (ICER) of $255,245 per QALY in Canada and €154,593 per QALY in France, which is comparable to other approved therapies for the same condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France. Karampampa, K., Zhang, W., Venkatachalam, M., et al.[2023]

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]

Cereblon is a key target for the immunomodulatory drugs lenalidomide and pomalidomide in treating multiple myeloma, suggesting it could serve as a predictive biomarker for therapy response or resistance.

The study developed a highly sensitive cereblon monoclonal antibody (CRBN65) and found that conventional methods for measuring cereblon levels may be inadequate, highlighting the need for standardized assays to accurately evaluate its role in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity. Gandhi, AK., Mendy, D., Waldman, M., et al.[2022]

Lenalidomide, an immunomodulatory drug used to treat multiple myeloma, has been associated with an increased risk of developing secondary primary malignancies, including high-grade astrocytomas like glioblastoma multiforme, as evidenced by a case study of a 72-year-old man.

This case marks the first reported instance of glioblastoma multiforme occurring after lenalidomide treatment in a patient with multiple myeloma, highlighting the need for awareness of this potential risk among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma Multiforme in a Patient with Multiple Myeloma: A Case Report and Literature Review. Moore, CA., Ibrahim, M., Kapila, A., et al.[2019]

References

1. 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]

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

Current treatment strategies with lenalidomide in multiple myeloma and future perspectives. [2018]

3. Slovakia pubmed.ncbi.nlm.nih.gov

Lenalidomide and dexamethasone in treatment of patients with relapsed and refractory multiple myeloma - analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

How lenalidomide is changing the treatment of patients with multiple myeloma. [2013]

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

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

6. 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]

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

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

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

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

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

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

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

Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France. [2023]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity. [2022]

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

Glioblastoma Multiforme in a Patient with Multiple Myeloma: A Case Report and Literature Review. [2019]