bb2121 for Multiple Myeloma

(KarMMa-2 Trial)

Recruiting at 41 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Must be taking: Proteasome inhibitors, Immunomodulatory agents

Must not be taking: Chronic immunosuppressants

Disqualifiers: CNS involvement, Plasma cell leukemia, 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: Single infusion

264 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in participants with relapsed and refractory multiple myeloma (RRMM) (Cohort 1), in participants with RRMM who receive bridging therapy with talquetamab (Cohort 1b), in participants with multiple myeloma (MM) having progressed within 18 months of initial treatment with autologous stem cell transplantation (ASCT) (Cohort 2a) and without ASCT (Cohort 2b) or, in participants with inadequate response post ASCT during initial treatment (Cohort 2c) and the efficacy and safety of bb2121 used in combination with lenalidomide maintenance in participants with suboptimal response post ASCT (Cohort 3). Approximately 264 participants will be enrolled into one of three cohorts. Cohort 1 (including cohort 1b) will enroll approximately 126 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently. Cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (NDMM) participants with suboptimal response to ASCT.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot use any systemic anti-myeloma drug therapy within 14 days before certain procedures in the trial. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have used any investigational agents or systemic anti-myeloma drug therapy within 14 days before certain trial procedures.

What data supports the idea that bb2121 for Multiple Myeloma is an effective treatment?

The available research shows that bb2121, also known as idecabtagene vicleucel or ide-cel, is an effective treatment for Multiple Myeloma. In a study comparing ide-cel to conventional care, ide-cel improved the overall response rate, meaning more patients responded positively to the treatment. It also increased the time patients lived without the disease getting worse and improved overall survival, which means patients lived longer compared to those receiving conventional care. These results suggest that ide-cel offers significant improvements in clinical outcomes for patients who have already tried many other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment idecabtagene vicleucel (ide-cel) for multiple myeloma?

Research shows that idecabtagene vicleucel (ide-cel) improves overall response rates, progression-free survival, and overall survival in patients with relapsed and refractory multiple myeloma compared to conventional care. It has been approved by the FDA and offers hope for more durable remissions and better quality of life for patients who have limited treatment options. ^{1 2 3 4 5}

What safety data is available for Idecabtagene Vicleucel (bb2121) in treating Multiple Myeloma?

Idecabtagene vicleucel (bb2121) has been evaluated for safety in multiple studies. In a single-arm trial, serious adverse reactions occurred in 67% of patients, with grade 3 or higher cytokine release syndrome and neurologic toxicities in 9% and 4% of patients, respectively. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4% of patients, with two fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% of patients, also with two fatalities. A phase 1 trial reported low rates of grade 3/4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). These studies confirm the safety and tolerability of ide-cel, with expected CAR T-cell therapy toxic effects. ^{1 4 6 7 8}

Is idecabtagene vicleucel (bb2121) safe for humans?

Idecabtagene vicleucel (bb2121) has been studied for safety in patients with multiple myeloma. Serious side effects occurred in 67% of patients, including severe immune reactions and nerve problems in a small percentage, with some cases leading to fatalities. However, the treatment is generally considered safe with manageable side effects for most patients. ^{1 4 6 7 8}

Is the treatment bb2121 (also known as Idecabtagene vicleucel, Abecma, ide-cel) a promising treatment for Multiple Myeloma?

Yes, bb2121, also known as Idecabtagene vicleucel or ide-cel, is a promising treatment for Multiple Myeloma. It has shown strong results in patients who have not responded to other treatments, with many experiencing significant and lasting improvements. It is approved by the FDA and has been effective in clinical trials. ^{1 3 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 (BCMA) on cancer cells, offering deep and durable responses for patients who have relapsed or are resistant to other treatments. ^{1 3 8 9 10}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults over 18 with Multiple Myeloma that's come back or didn't respond to treatment, including those who've had a stem cell transplant. It's not for those who've recently used investigational drugs, have certain medical conditions like organ failure or uncontrolled infections, are pregnant or breastfeeding, or have a history of blood clots.

Inclusion Criteria

I am 18 years or older.

Participants need to meet specific requirements for the type of multiple myeloma they have.

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

Exclusion Criteria

I haven't had certain treatments in the 2 weeks before my leukapheresis or giving consent.

I do not have a history of severe illnesses, infections, or other health conditions listed.

Subject used any investigational agents within 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bridging Therapy

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a, and 2b

Variable

Treatment

Participants receive bb2121 autologous CAR T cells infusion after lymphodepleting chemotherapy

Single infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• bb2121

Trial Overview The study tests bb2121 and Lenalidomide in different groups: one with relapsed/refractory myeloma after multiple treatments; others with early relapse post-transplant; and some with inadequate response to initial transplant therapy. The goal is to see how well these treatments work and their safety.

Participant Groups

Group I: Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma Experimental Treatment 2 Interventions

Group II: Cohort 2c: BB2121 in multiple myeloma participants with inadequate response post ASCT Experimental Treatment 1 Intervention

Group III: Cohort 2b: BB2121 in multiple myeloma without Autologous stem cell transplantation participants Experimental Treatment 1 Intervention

Group IV: Cohort 2a: BB2121 in multiple myeloma with Autologous stem cell transplantation participants Experimental Treatment 1 Intervention

Group V: Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants Experimental Treatment 2 Interventions

Group VI: Cohort 1: BB2121 in relapsed and refractory multiple myeloma participants Experimental Treatment 1 Intervention

bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy

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

Approved in European Union as Abecma for:

• Relapsed or refractory multiple myeloma

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

Findings from Research

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 52 patients treated with idecabtagene vicleucel (ide-cel) for relapsed/refractory multiple myeloma, 65% experienced grade ≥ 3 cytopenias by day 30, indicating significant blood cell reductions, which required interventions like G-CSF and transfusions for many patients.

Infections were reported in 54% of patients, with 23% being severe; early infections were mostly bacterial, while later infections included both bacterial and viral types, highlighting the need for careful monitoring and management of infections post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. Logue, JM., Peres, LC., Hashmi, H., et al.[2022]

Patients with multiple myeloma who do not respond to existing therapies have limited survival, but new treatments like CAR T-lymphocytes, bispecific antibodies, and antibody-drug conjugates are showing promise in early trials.

Idecabtagene vicleucel (ide cel) and belantamab mafodotin (belamaf) have been approved for use in relapsed/refractory multiple myeloma based on positive results from phase 2 studies, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. Lakshman, A., Kumar, SK.[2022]

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]

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) 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]

The introduction of new drug classes, including CAR-T therapy targeting BCMA, has significantly improved the 5-year survival rate of multiple myeloma patients, doubling it over the past two decades.

Idecabtagene vicleucel (ide-cel) is the first CAR-T therapy approved for treating relapse or refractory multiple myeloma, showing promising clinical efficacy and relatively lower toxicity, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel for relapsed/refractory multiple myeloma: a review of recent advances. Tu, W., Xiao, Y., Wang, Y., 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. United States pubmed.ncbi.nlm.nih.gov

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

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

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. [2022]

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

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. [2022]

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

9. Spain pubmed.ncbi.nlm.nih.gov

Idecabtagene vicleucel for relapsed/refractory multiple myeloma: a review of recent advances. [2022]

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

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