Ide-cel (bb2121) for Multiple Myeloma

Overseen By Sergio Giralt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Organ transplant, CNS pathology, 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: Unknown

Duration: 1 year

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see if the quality of T cells used to create ide-cel (bb2121) affects how ide-cel prevents cancer from coming back in people with relapsed or refractory multiple myeloma (MM), and who have had a hematopoietic cell transplant.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-myeloma therapy 14 days before leukapheresis (a procedure to collect blood cells), and you must taper off steroids 72 hours before leukapheresis and lymphodepletion (a process to reduce white blood cells). Other medications may be allowed, but it's best to discuss your specific situation with the trial team.

What data supports the effectiveness of the treatment Ide-cel (bb2121) for Multiple Myeloma?

Research shows that Ide-cel, a type of CAR T-cell therapy, is effective for patients with relapsed and refractory multiple myeloma, with a high overall response rate of about 75.8% and a complete response rate of 38.7%. It also improves survival outcomes compared to conventional care, offering hope for patients who have not responded to other treatments. ^{1 2 3 4 5}

What is known about the safety of Ide-cel (bb2121) for treating multiple myeloma?

Ide-cel (bb2121) has been studied for safety in treating multiple myeloma, showing low rates of severe 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). Some patients experienced cardiac events like heart failure and atrial fibrillation, especially those with poor health status or higher-grade immune reactions. ^{1 2 5 6 7}

What makes the treatment Ide-cel unique for multiple myeloma?

Ide-cel is a unique treatment for multiple myeloma because it is a CAR T-cell therapy that targets a specific protein called B-cell maturation antigen (BCMA) on cancer cells. This approach allows for a single infusion that can lead to deep and durable responses, offering hope for patients who have not responded to other treatments. ^{1 2 4 5 8}

Research Team

Gunjan Shah, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with multiple myeloma who've had a cell transplant and at least four prior treatments including specific drugs. They must have recovered from previous treatment side effects, not be on certain medications, and agree to birth control measures. Pregnant or breastfeeding women, those with severe heart conditions or active infections, and individuals with other cancers are excluded.

Inclusion Criteria

I have MM, treated with 4+ lines including IMID, PI, CD38 antibody, had allo HCT, and show minimal disease post 3 months of HCT.

Your liver and heart function tests must be within a certain range, and you need to commit to regular study visits and follow-up for 15 years.

I agree to use protection during sex and not donate sperm for 1 year after my treatment.

Exclusion Criteria

You had certain medical procedures or conditions within a specific time frame, have certain medical conditions, are taking certain medications, or have certain infections, which would prevent you from taking part in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive high doses of chemotherapy to kill cancer cells and prepare for stem cell transplantation

2-3 weeks

Transplantation

Participants undergo autologous or allogeneic hematopoietic cell transplantation

1-2 weeks

Treatment

Manufacturing and administration of Ide-Cel (bb2121) to prevent cancer recurrence

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Ide-cel (bb2121)

Trial Overview The study tests if T cells used to create the drug ide-cel (bb2121) can prevent cancer recurrence in patients with relapsed/refractory multiple myeloma post-cell transplant. It examines the quality of T cells' impact on ide-cel's effectiveness.

Participant Groups

Group I: Cohort 2 Experimental Treatment 1 Intervention

Participants with relapsed/refractory MM who had an allogeneic hematopoietic cell transplant (alloHCT). In an alloHCT, a person's stem cells are replaced with new, healthy stem cells from a donor.

Group II: Cohort 1 Experimental Treatment 1 Intervention

Participants with relapsed/refractory MM who had an autologous hematopoietic stem cell transplant (AHCT). In an AHCT, their own blood-forming stem cells are collected. Participants are then treated with high doses of chemotherapy which kills the cancer cells, but it also gets rid of the blood-producing cells that are left in the bone marrow. Afterward, the collected stem cells are put back into the bloodstream, allowing the bone marrow to produce new blood cells.

Ide-cel (bb2121) 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 4 or more prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody

Approved in European Union as Abecma for:

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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) 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) 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]

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]

In a study of 78 patients treated with idecabtagene vicleucel (ide-cel) for relapsed and refractory multiple myeloma, 14.1% experienced cardiac events, including heart failure and atrial fibrillation, indicating a notable safety concern associated with this CAR-T therapy.

Higher-grade cytokine release syndrome and poor baseline performance status were linked to an increased risk of cardiac events, which in turn were associated with worse overall survival and progression-free survival, suggesting that monitoring for cardiac complications is important in patients receiving ide-cel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma. Lee, DH., Kumar, A., Mohammed, T., et al.[2023]

Idecabtagene vicleucel (ide-cel) is an effective CAR T cell therapy for heavily pretreated relapsed and refractory multiple myeloma, showing higher response rates with increased exposure levels in a study of 127 patients.

The analysis identified specific factors, such as female sex and lower baseline serum monoclonal protein levels, that predict better treatment responses, while also establishing a positive benefit-risk profile for ide-cel doses ranging from 150 to 450 million CAR+ T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. Connarn, JN., Witjes, H., van Zutphen-van Geffen, M., 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]

References

1. 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]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma. [2023]

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

Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. [2023]

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

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