Ide-cel (bb2121) for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Anticoagulants, Immunosuppressants
Disqualifiers: Organ transplant, CNS pathology, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
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.12345
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.12567
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.12458
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.
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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.
Trial 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) (CAR T-cell Therapy)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: Cohort 2Experimental Treatment1 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 1Experimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. [2023]Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929 .
Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. [2023]Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label.
Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. [2022]Aim: To compare the efficacy of idecabtagene vicleucel (ide-cel, bb2121) versus conventional care (CC) in triple-class exposed relapsed and refractory multiple myeloma (RRMM) patients. Patients & methods: A matching-adjusted indirect comparison was conducted using individual patient-level data from the pivotal, phase II, single-arm KarMMa trial (NCT03361748) and aggregate-level data from MAMMOTH, the largest independent observational study of CC in heavily pretreated RRMM patients. Results: Ide-cel improved overall response rate (odds ratio: 5.30; 95% CI: 2.96-9.51), progression-free survival (hazard ratio: 0.50; 95% CI: 0.36-0.70) and overall survival (hazard ratio: 0.37; 95% CI: 0.25-0.56) versus CC. Conclusion: These results suggest ide-cel offers improvements in clinical outcomes relative to CC in this heavily pretreated RRMM population.
Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma. [2022]Idecabtagene vicleucel (ide-cel), a novel chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), has recently gained approval by the US FDA for relapsed and refractory multiple myeloma (RRMM) after multicenter trials have demonstrated unprecedented results in this difficult-to-treat subgroup of patients. As the first CAR T-cell product approved for myeloma, ide-cel is poised to become a practice-changing treatment option. This first-in-class therapeutic offers hope for more durable remissions, as well as better quality of life, following a single infusion in a group of patients that previously had little hope. This paper reviews the ide-cel product in terms of design, pharmacology, efficacy and toxicity as described in studies reported to date.
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. [2021]Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma.
Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma. [2023]Idecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CAR-T) approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Currently, the incidence of cardiac events associated with ide-cel remains unclear. This was a retrospective single-center observational study of patients treated with ide-cel for RRMM. We included all consecutive patients who received standard-of-care ide-cel treatment at least 1-month follow-up. Baseline clinical risk factors, safety profile, and responses were examined based on the development of a cardiac event. A total of 78 patients were treated with ide-cel, and 11 patients (14.1%) developed cardiac events: heart failure (5.1%), atrial fibrillation (10.3%), nonsustained ventricular tachycardia (3.8%), and cardiovascular death (1.3%). Only 11 of the 78 patients had repeat echocardiogram. Baseline risk factors associated with the development of cardiac events included being female sex and having poor performance status, λ light-chain disease, and advanced Revised International Staging System stage. Baseline cardiac characteristics were not associated with cardiac events. During index hospitalization after CAR-T, higher-grade (≥grade 2) cytokine release syndrome (CRS) and immune cell-associated neurologic syndrome were associated with cardiac events. In multivariable analyses, the hazard ratio for the association of the presence of cardiac events with overall survival (OS) was 2.66 and progression-free survival (PFS) was 1.98. Ide-cel CAR-T for RRMM was associated with similar cardiac events as other types of CAR-T. Worse baseline performance status and higher-grade CRS and neurotoxicity were associated with cardiac events after BCMA-directed CAR-T-cell therapy. Our results suggest that the presence of cardiac events may confer worse PFS or OS; although because of the small sample size, the power to detect an association was limited.
Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. [2023]Idecabtagene vicleucel (ide-cel; bb2121) is a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy approved for treatment of patients with heavily pretreated relapsed and refractory multiple myeloma. This analysis evaluated exposure-response (ER) relationships of ide-cel with key efficacy end points and safety events. Ide-cel exposure data were available from 127 patients treated at target doses of 150, 300, or 450 × 106 CAR+ T cells from the phase II KarMMa study (NCT03361748). Key exposure metrics, including area under the curve of the transgene level from 0 to 28 days and maximum transgene level, were calculated using noncompartmental methods. Logistic regression models, using both linear and maximum response function of exposure on the logit scale, were evaluated to quantify observed ER trends, and modified by including statistically significant individual covariates in a stepwise regression analysis. There was wide overlap of exposures across the target doses. ER relationships were observed for the overall and complete response rates, with higher response rates associated with higher exposures. Model-based evaluations identified female sex and baseline serum monoclonal protein less than or equal to 10 g/L as predictive of a higher objective response rate and a higher complete response rate, respectively. ER relationships were observed for safety events of cytokine release syndrome requiring tocilizumab or corticosteroids. The established ER models were used to quantify the ide-cel dose-response, which showed a positive benefit-risk assessment for the range of ide-cel exposures associated with the target dose range of 150-450 × 106 CAR+ T cells.
Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. [2023]Survival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma.