A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy

Titre officiel

A Phase 3 Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy

Sommaire:

Cette étude a pour but de comparer, en fonction de la survie sans progression (SSP), l’efficacité du traitement d’induction selon le protocole VRD (bortézomib, lénalidomide et dexaméthasone), suivi de l’administration d’une dose unique de ciltacabtagène autoleucel (cilta-cel), à l’efficacité du traitement d’induction VRD suivi d’un traitement d’entretien par la lénalidomide et la dexaméthasone (RD) chez des participants atteints d’un myélome multiple récemment diagnostiqué pour qui l’autogreffe de cellules souches n’est pas le traitement initial prévu.

Description de l'essai

Primary Outcome:

• Progression Free Survival (PFS)

Secondary Outcome:

• Sustained Minimal Residual Disease (MRD) Negative CR
• MRD Negative CR at 9 Months
• Overall MRD Negative CR
• Overall Survival (OS)
• Complete Response or Better
• Time to Subsequent Anti-myeloma Therapy
• Progression Free Survival on Next-line Therapy (PFS2)
• Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs
• Arm B: Systemic Cytokine Concentrations
• Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers
• Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA)
• Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence
• Arm B: Number of Participants with Anti-cilta-cel Antibodies
• Arm B: Number of Participants with Presence of Replication Competent Lentivirus
• Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
• Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score
• Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score
• Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
• Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items
• Time to Worsening of Symptoms, Functioning and Overall Well-being

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B lymphocytes and malignant plasma cells. The primary hypothesis of this study is that in participants with newly diagnosed MM, treatment with VRd induction followed by a single administration of cilta-cel will significantly improve progression free survival compared to Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by Rd maintenance. The study will screen participants with newly diagnosed MM who are not planned to receive autologous stem cell transplant (ASCT) as initial therapy. This study will be conducted in 4 phases: Screening (up to 28 days), Pre-randomization Treatment, Treatment, and Follow-up. Assessments like patient-reported outcome(s) (PROs), electrocardiogram (ECG), vital signs and pharmacokinetics will be performed during the study. Safety evaluations will include review of adverse events, laboratory test results, vital sign measurements, physical examination findings, assessment of cardiac function, Immune-Effector Cell-Associated Encephalopathy (ICE) and handwriting assessments (only for Arm B) and Eastern Cooperative Oncology Group (ECOG) performance status. Safety data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 12 years 5 months.

Voir cet essai sur ClinicalTrials.gov