A Study to Compare the Efficacy and Safety of Idecabtagene Vicleucel With Lenalidomide Maintenance Therapy Versus Lenalidomide Maintenance Therapy Alone in Adult Participants With Newly Diagnosed Multiple Myeloma Who Have Suboptimal Response After Autologous Stem Cell Transplantation

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Idecabtagene Vicleucel With Lenalidomide Maintenance Versus Lenalidomide Maintenance Therapy Alone in Adult Participants With Newly Diagnosed Multiple Myeloma Who Have Suboptimal Response After Autologous Stem Cell Transplantation (KarMMa-9)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: idecabtagene vicleucel
* Drug: Lenalidomide
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged ≥18 with Newly Diagnosed Multiple Myeloma (NDMM) who has received induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), without subsequent consolidation or maintenance. EXCEPTION: Participant received ≤ 7 days of lenalidomide (LEN) maintenance therapy and the investigator documents that there is no impact to the overall benefit/risk assessment due to the temporary interruption of LEN. Participant must have received 4 to 6 cycles of induction therapy, which must contain at a minimum an immunomodulatory drugs (IMiD) and a proteasome inhibitor (PI) (with or without anti-CD38 monoclonal antibody) and must have had a single ASCT 80 to 120 days prior to consent. Note: Participant must not have confirmed progression since commencing induction. Participant must have documented response of PR or VGPR at time of consent. Participant must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (participants with ECOG 2 due to pain because of underlying myeloma-associated bone lesions are eligible per investigator's discretion). Participant must have recovered to ≤ Grade 1 for any nonhematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy. Exclusion Criteria: Participant with known central nervous system involvement with myeloma. Participant has non-secretory MM. Participant has systemic and uncontrolled fungal, bacterial, viral, or other infection. Participant has history of primary immunodeficiency. Participant has previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or B-cell maturation antigen targeted therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Biological: idecabtagene vicleucel<br>* Specified dose on specified days<br>* Other names: ide-cel;Drug: Lenalidomide<br>* Specified dose on specified days<br>* Other names: LEN;Drug: Fludarabine<br>* Specified dose on specified days<br>* Other names: BENDARBIN;Drug: Cyclophosphamide<br>* Specified dose on specified days<br>* Other names: CYTOXAN;|
| Active Comparator: Arm B<br> | Drug: Lenalidomide<br>* Specified dose on specified days<br>* Other names: LEN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS as assessed by Independent Review Committee (IRC) | Up to approximately 49 months after the first participant is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Up to approximately 60 months after the last participant is randomized | 
| Percentage of Participants with Sustained Minimal Residual Disease Negative (MRDneg) Complete Response (CR) for 12 months |  | From randomization up to 27 months from randomization | 
| Percentage of Participants with Minimal Residual Disease Negative (MRDneg) Complete Response (CR) |  | From randomization up to 15 months from randomization | 
| Event-Free Survival (EFS) |  | Up to approximately 60 months after the last participant is randomized | 
| Duration of Response (DOR) |  | Up to approximately 60 months after the last participant is randomized | 
| Percentage of Participants with Complete Response (CR) | CR as assessed by IRC | Up to approximately 60 months after the last participant is randomized | 
| Time to Progression (TTP) | Progression as assessed by IRC | Up to approximately 60 months after the last participant is randomized | 
| Progression post-next line of treatment (PFS2) |  | Up to approximately 60 months after the last participant is randomized | 
| Time to Next Treatment (TTNT) |  | Up to approximately 60 months after the last participant is randomized | 
| Number of Participants Experiencing Adverse Events (AEs) |  | Up to approximately 60 months after the last participant is randomized | 
| Number of Participants Experiencing Adverse Events of Special Interest (AESI) |  | Up to approximately 60 months after the last participant is randomized | 
| Maximum Observed Plasma Concentration (Cmax) |  | Up to approximately 60 months after the last participant is randomized | 
| Time of Maximum Observed Plasma Concentration (Tmax) |  | Up to approximately 60 months after the last participant is randomized | 
| Area Under the Curve (AUC) from time zero to 28 days post infusion (AUC [0- 28D]) |  | Up to 28 days post infusion | 
| Time of Last Measurable Observed Plasma Concentration (Tlast) |  | Up to approximately 60 months after the last participant is randomized | 
| Time-to-Definitive Deterioration | Time-to-definitive deterioration based on the European Organization for Research and Treatment of Cancer core quality of life questionnaire EORTC QLQ-C30 global health status/quality of life subscale | Up to approximately 49 months after the first participant is randomized | 
| Mean Change from Baseline in EORTC QLQ-C30 Selected Subscales | The following subscales on the European Organization for Research and Treatment of Cancer core quality of life questionnaire EORTC QLQ-C30 will be assessed: Global health status/quality of life Physical Functioning Fatigue Pain | Up to approximately 49 months after the first participant is randomized | 
| Mean Change from Baseline in EORTC QLQ-MY20 Selected Subscales | The following subscales on the European Organization for Research and Treatment of Cancer core quality of life questionnaire EORTC QLQ-MY20 will be assessed: Disease symptoms Side-effects of treatment | Up to approximately 49 months after the first participant is randomized | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T