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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with multiple myeloma, a type of blood cancer. Researchers aim to determine if adding a new drug, ide-cel (Idecabtagene Vicleucel), to the standard treatment with lenalidomide increases effectiveness. The study compares the two treatments to assess which works better and is safer. Suitable participants have recently been diagnosed with multiple myeloma and have received certain intensive treatments, including a stem cell transplant, but have not yet undergone further treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that idecabtagene vicleucel (ide-cel), when combined with lenalidomide (LEN), is generally safe. In studies involving multiple myeloma patients, ide-cel extended the time patients lived without disease progression and improved their response to treatment compared to standard options. Patients generally tolerated the treatment well.

Real-world evidence supports these findings, confirming ide-cel's safety and effectiveness in patients whose multiple myeloma has returned or not responded to other treatments. Some patients experienced side effects, but these were similar to those observed in clinical trials and could be managed.

Overall, these studies suggest that ide-cel, both alone and with LEN, is generally safe, with a safety profile similar to other multiple myeloma treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about Idecabtagene Vicleucel (ide-cel) for multiple myeloma because it offers a novel approach by using a patient's own immune cells to fight cancer. Unlike traditional treatments like chemotherapy or proteasome inhibitors, ide-cel is a type of CAR-T cell therapy that genetically modifies T cells to target and destroy myeloma cells specifically. This method not only provides a new mechanism of action but also has the potential for long-lasting remission with just a single infusion. Furthermore, combining ide-cel with Lenalidomide, an immunomodulatory drug, enhances the immune response and may improve the treatment's effectiveness, offering hope for patients with this challenging condition.

What evidence suggests that this trial's treatments could be effective for Multiple Myeloma?

Research has shown that idecabtagene vicleucel (ide-cel) may effectively treat multiple myeloma, particularly in patients whose cancer has returned or did not respond to other treatments. In a large study, ide-cel helped many patients achieve remission, with no signs of cancer detected. In this trial, some participants will receive ide-cel alone, while others will receive ide-cel combined with lenalidomide, a drug that boosts the immune system. This combination aims to improve outcomes for patients who did not respond well after a stem cell transplant. Strong results from earlier studies suggest this treatment could offer hope for people newly diagnosed with multiple myeloma. ^{1 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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) 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 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]

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]

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) 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 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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06045806

NCT06045806 | A Study to Compare the Efficacy and ... 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 ...

2. ashpublications.org ashpublications.org/blood/article/146/2/167/536610/Standard-of-care-idecabtagene-vicleucel-for

Standard-of-care idecabtagene vicleucel for relapsed ... Largest real-world study of ide-cel in R/R MM shows favorable safety and efficacy profile that mirrors trial experience.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19532

Real-world analysis of overall survival and time to next ... Comparative efficacy of idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma: Real-world analysis of ...

4. abecma.com abecma.com/is-abecma-right-for-me/abecma-results

ABECMA® Clinical Trial Results In a clinical study of 386 people with relapsed/refractory multiple myeloma, 254 people received ABECMA and 132 people received standard treatment.† Everyone ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125008523

Standard-of-care idecabtagene vicleucel for relapsed/ ... In conclusion, ide-cel demonstrated a favorable safety and efficacy profile in the real-world setting, comparable with a pivotal registration ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024016902

MM-493 Efficacy and Safety of Idecabtagene Vicleucel (ide ... Ide-cel, a BCMA-directed CAR T-cell therapy, significantly improved median PFS and ORR versus standard regimens in TCE RRMM. Ide-cel also showed deep, durable ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06698887

A Study to Evaluate the Long-Term Safety of Idecabtagene ... The purpose of this study is to monitor the long-term safety of participants who received idecabtagene vicleucel treatment as part of the KarMMa-9 (CA089-1043) ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571575/

Patient-Reported Outcomes among Multiple Myeloma ... Patient-reported outcomes among multiple myeloma patients treated with standard of care Idecabtagene Vicleucel.