Ide-cel + Lenalidomide for Multiple Myeloma (KarMMa-9 Trial)
Recruiting in Palo Alto (17 mi)
+114 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Celgene
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?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 in adult participants with Newly Diagnosed Multiple Myeloma (NDMM) who have achieved a suboptimal response post autologous stem cell transplantation (ASCT).
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.
What data supports the effectiveness of the drug Lenalidomide for treating multiple myeloma?
Lenalidomide, when combined with dexamethasone, has been shown to improve response rates and extend survival in patients with relapsed or refractory multiple myeloma, as demonstrated in pivotal phase III trials. This combination is effective in improving overall survival and progression-free survival compared to dexamethasone alone.
12345Is the Ide-cel + Lenalidomide treatment safe for humans?
Research shows that Idecabtagene vicleucel (ide-cel) is generally safe for humans, with low rates of serious side effects like 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).
678910What makes the drug Ide-cel + Lenalidomide unique for treating multiple myeloma?
Idecabtagene Vicleucel (Ide-cel) is a type of CAR T-cell therapy, which is a personalized treatment that uses a patient's own immune cells to target and destroy cancer cells. This approach is different from traditional drugs like lenalidomide, which modulate the immune system more broadly.
35111213Eligibility Criteria
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
I have recovered from previous treatment side effects, except for hair loss and mild nerve pain.
Exclusion Criteria
I do not have any uncontrolled infections.
My myeloma has spread to my brain or spinal cord.
My multiple myeloma does not produce detectable levels of M protein.
I have had a stem cell transplant or gene/cell therapy for cancer.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm AExperimental Treatment4 Interventions
Group II: Arm BActive Control1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Northside HospitalAtlanta, GA
Banner MD Anderson Cancer CenterGilbert, AZ
Mayo Clinic in FloridaJacksonville, FL
Houston Methodist HospitalHouston, TX
More Trial Locations
Loading ...
Who is running the clinical trial?
CelgeneLead Sponsor
Bristol-Myers SquibbIndustry Sponsor
References
Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. [2020]As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.
Current treatment strategies with lenalidomide in multiple myeloma and future perspectives. [2018]Lenalidomide is an immunomodulatory drug derived from thalidomide, developed to maximize its anti-inflammatory and antineoplastic properties while reducing toxicity. Lenalidomide administered orally at 25 mg/d on days 1-21 of 28-day cycles plus dexamethasone is indicated for the treatment of relapsed/refractory multiple myeloma patients, who received at least one prior therapy. In the pivotal MM-009 and MM-010 Phase III registration trials, lenalidomide-dexamethasone, when compared with placebo-dexamethasone, significantly improved response rate (60 vs 20%, respectively), time-to-progression and survival. The most common adverse events included hematologic toxicity and venous thromboembolism. The drug is currently being investigated for the treatment of newly diagnosed myeloma and, in association with chemotherapy drugs (cyclophosphamide and melphalan) or novel agents (bortezomib, carfilzomib and elotuzumab), for the development of highly active combination regimens.
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. [2019]Lenalidomide (LEN) is an immunomodulator with clinical activity against myeloma cells. Based on the pivotal phase 3 trials MM-009 and MM010, the combination of lenalidomide and dexamethasone(DEX) was approved for patients with multiple myeloma who received at least one prior therapy. Here, we evaluated LEN/DEX therapy in unselected population and subsequently in selected sub-groups of patients with relapsed/refractory multiple myeloma followed in the Registry of Monoclonal Gammopathies of the Czech Myeloma Group. Altogether 858 patients were treated with LEN/DEX in the Czech Republic and Slovakia until end of 2017. The analyzed sub-groups were defined as patients with high risk cytogenetic aberrations and patients with relapsed and refractory MM. The overall response rate (ORR; partial remission or better response, PR) in the whole group of patients was 46.3% for all lines of therapy, 26.4% for high-risk group and 32.1% for relapsed and refractory group. Medians of overall survival (OS) in the same cohorts were as follows: 25.6, 15.7 and 18.5 months, progression free survival (PFS) was: 11.2, 6.4 and 9.0 months respectively. The most common adverse events were hematologic and infectious. In conclusion we found that our results correlated with those found in other studies in terms of response rates, survival measures, and also of treatment toxicity.
How lenalidomide is changing the treatment of patients with multiple myeloma. [2013]Lenalidomide is a distinct second-generation immunomodulatory drug with multiple anticancer and immunomodulatory effects against hematologic malignancies, in particular multiple myeloma (MM). Dexamethasone synergistically enhances the anticancer effects of lenalidomide, and the combination of lenalidomide and dexamethasone (Len/Dex) is approved for the treatment of patients with relapsed and/or refractory MM. Results from pivotal phase III trials in this setting have demonstrated that Len/Dex extends overall survival compared with dexamethasone alone. Optimal clinical benefits are seen when Len/Dex is initiated at first relapse and continued, beyond best treatment response, until disease progression. Lenalidomide based regimens are also effective as induction therapy in patients with newly diagnosed MM. Importantly, lenalidomide has a predictable and manageable tolerability profile, with minimal neurotoxicity, allowing long-term administration. As the paradigm of myeloma disease continues to change, future studies will determine the efficacy of lenalidomide in novel combinations with potentially complimentary agents.
Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. [2021]To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses.
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 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.
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.
Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France. [2023]The chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel) is approved for the treatment of adult patients with relapsed/refractory multiple myeloma (RRMM) who have already received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have progressed on their last therapy. The objective of this study was to assess the cost-effectiveness of ide-cel versus conventional care in Canada and France.
Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. [2020]Bortezomib- and lenalidomide-containing regimens are well-established therapies in multiple myeloma (MM). However, despite their extensive use, head-to-head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed-duration therapies. In this open-label, phase III study, we randomized MM patients at first relapse to receive either nine cycles of bortezomib plus cyclophosphamide plus dexamethasone (VCD) or lenalidomide plus cyclophosphamide plus dexamethasone (RCD). The primary endpoint was achievement of a very good partial response (VGPR) or better at six weeks after nine treatment cycles. From March 2011 to February 2015, 155 patients were randomized. VGPR or better was achieved by 12 patients (15%) in the VCD arm and 14 patients (18%) in the RCD arm (P = 0·70). Median progression-free survival (PFS) was 16·3 (95% CI: 12·1-22·4) with VCD and 18·6 months (95% CI: 14·7-25·5) with RCD, and the two-year overall survival (OS) was 75% (95% CI: 66-86%) and 74% (95% CI: 64-85%) respectively. In subgroup analyses, no differences in PFS were observed in bortezomib- and lenalidomide-naïve patients, nor in patients who received a bortezomib-based regimen in first line. Adverse events were consistent with the well-established safety profiles of both drugs. Bortezomib and lenalidomide treatments were equally effective in terms of depth of response, PFS, and OS in MM patients at first relapse.
Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity. [2022]Cereblon, a member of the cullin 4 ring ligase complex (CRL4), is the molecular target of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (MM) and immunomodulatory activity in T cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to IMiD therapy. Our studies characterized a cereblon monoclonal antibody CRBN65, with high sensitivity and specificity in Western analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both MM cell lines and primary cells, highlighting challenges with conventional gene expression assays given this gene complexity. Using CRBN65 antibody and TaqMan quantitative reverse transcription polymerase chain reaction assays, we showed lack of correlation between cereblon protein and mRNA levels. Furthermore, lack of correlation between cereblon expression in MM cell lines and sensitivity to lenalidomide was shown. In cell lines made resistant to lenalidomide and pomalidomide, cereblon protein is greatly reduced. These studies show limitations to the current approaches of cereblon measurement that rely on commercial reagents and assays. Standardized reagents and validated assays are needed to accurately assess the role of cereblon as a predictive biomarker.
Glioblastoma Multiforme in a Patient with Multiple Myeloma: A Case Report and Literature Review. [2019]Lenalidomide is an immunomodulatory drug approved by the US Food and Drug Administration in 2006 for the treatment of multiple myeloma. In 2012, the Food and Drug Administration issued a statement warning physicians of the increased risk with lenalidomide treatment of the following secondary primary malignancies: Acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma. The statement did not mention glioblastoma multiforme, a Grade 4 astrocytoma, or other high-grade astrocytomas that have been reported on rare occasions in the setting of multiple myeloma.