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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the quality of T cells used in the treatment ide-cel (a type of CAR T-cell therapy) affects its ability to prevent the return of multiple myeloma, a type of blood cancer. It targets patients whose cancer has returned or resisted treatment after a stem cell transplant. One group will have received their own stem cells, while the other will have received donor stem cells. Ideal participants have undergone multiple treatments and a stem cell transplant but still experience cancer symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that ide-cel (bb2121) is likely to be safe for humans?

Studies have shown that ide-cel (also known as bb2121) is generally well-tolerated in people with relapsed or refractory multiple myeloma. Research indicates that while some side effects occur, they are often manageable. For example, one study found that ide-cel treatment led to strong and lasting improvements in patients. However, like many cancer treatments, side effects can occur. The most common include low blood cell counts and infections, but these are usually expected and treatable. Overall, the treatment has shown promise in terms of safety and effectiveness. ^{1 2 3 4 5}

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

Researchers are excited about Ide-cel (bb2121) for multiple myeloma because it uses a cutting-edge approach known as CAR-T cell therapy. Unlike traditional treatments like chemotherapy and proteasome inhibitors, which attack cancer cells broadly, Ide-cel reprograms a patient's own immune cells to specifically target and destroy myeloma cells. This personalized approach has the potential to offer more targeted and effective treatment for patients who have relapsed or not responded to other therapies. Additionally, there are two distinct delivery methods being explored: one involves using the patient's own stem cells in an autologous transplant, and the other uses healthy donor stem cells in an allogeneic transplant, offering more options depending on individual patient situations.

What evidence suggests that ide-cel (bb2121) might be an effective treatment for multiple myeloma?

Research has shown that ide-cel (bb2121) holds great promise for treating relapsed or refractory multiple myeloma. In one study, 89% of patients responded well, with their cancer shrinking or disappearing. Another study demonstrated an 84% response rate, with over half of the patients experiencing a very deep remission, where the cancer was almost completely gone. These studies suggest that ide-cel can lead to significant and lasting improvements for many patients. In this trial, participants will be divided into two cohorts: one for those who had an autologous hematopoietic stem cell transplant (AHCT) and another for those who had an allogeneic hematopoietic cell transplant (alloHCT). The treatment uses modified T cells, a type of white blood cell, to find and destroy cancer cells. ^{1 3 4 6 7}

Who Is on the Research Team?

Gunjan Shah, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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 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]

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) 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 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) 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024850

Idecabtagene Vicleucel in Relapsed and Refractory ... Idecabtagene vicleucel (ide-cel, also called bb2121) showed promising efficacy in a phase 1 study involving patients with relapsed or refractory myeloma.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36690910/

Phase 2 results of idecabtagene vicleucel (ide-cel, bb2121 ... Results: Nine patients were treated with ide-cel. The overall response rate was 89% (median follow-up, 12.9 months). The best overall response was stringent ...

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

ABECMA® Clinical Trial Results See ABECMA® (idecabtagene vicleucel) clinical trial results for adults with relapsed/refractory multiple myeloma and how they responded to treatment.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19500

Outcomes of ide-cel in patients with relapsed/refractory ... The median follow-up was 11.4 months. The objective response rate was 84%; sCR was seen in 56% of patients, VGPR in 16%, PR in 12%, and PD in 16 ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2101/503044/Efficacy-and-Safety-of-Idecabtagene-Vicleucel-ide

Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in ... In cohort 2c, with a median follow-up of 27.9 months, ide-cel demonstrated deep and durable responses; complete response (CR) rate was 74.2% ( ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37592106/

post hoc 18-month follow-up of a phase 1 trial - PubMed - NIH These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.8016

Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed ... Ide-cel, a BCMA-directed CAR T cell therapy, showed frequent, deep, and durable responses in heavily pretreated pts with RRMM in the pivotal KarMMa trial.