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 (CARTITUDE-5)
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Newly Diagnosed Multiple Myeloma, Cellular Therapy, CAR-T Therapy, BCMA CAR-T
Eligibility Criteria
Inclusion Criteria:
- Documented diagnosis of multiple myeloma (MM) according to International Myeloma Working Group (IMWG) diagnostic criteria
- Measurable disease at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=)1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours; or Light chain MM in whom only measurable disease is by serum free light chain (FLC) levels: Serum immunoglobin (Ig) free light chain >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa/lambda FLC ratio
- Eastern Cooperative Oncology Group Performance Status grade of 0 or 1
- Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age; or Ineligible due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or Deferral of high-dose chemotherapy with ASCT as initial treatment
- A woman of childbearing potential (WOCBP) must have 2 negative highly sensitive serum or urine pregnancy tests (beta-human chorionic gonadotropin) prior to starting Bortezomib, Lenalidomide and Dexamethasone (VRd) and must agree to further testing during the study.
- Clinical laboratory values meeting the following criteria during the screening phase: hemoglobin greater than or equal to (>=) 8.0 g/dL (>=5 millimoles per liter [mmol/L]), recombinant human erythropoietin use is permitted; platelets >=75 *10^9/L; absolute lymphocyte count >=0.3 *10^9/L; absolute neutrophil count (ANC) >=1.0 ×10^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to (<=) 3.0 * upper limit of normal (ULN); estimated glomerular filtration rate >=40 milliliter per minute/1.73 meter square (mL/min/1.73 m^2) based upon modified diet in renal disease formula (MDRD-4) calculation or a 24-hour urine collection; total bilirubin <=2.0 * ULN; except in participants with congenital hyperbilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=2.0 * ULN is required)
Exclusion Criteria:
- Frailty index of >=2 according to Myeloma Geriatric Assessment score
- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5
- Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
- Stroke or seizure within 6 months of signing Informed Consent Form (ICF)
- Seropositive for human immunodeficiency virus (HIV)
- Vaccinated with live, attenuated vaccine within 4 weeks prior to first dose of VRd
- Participant must not require continuous supplemental oxygen
- Hepatitis B infection
- Hepatitis C infection
- Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
- Any therapy that is targeted to B-cell maturation antigen (BCMA)
Sites / Locations
- UCSFRecruiting
- Yale Cancer CenterRecruiting
- University of Miami Health SystemRecruiting
- AdventHealth Cancer InstituteRecruiting
- University of Iowa Hospitals & ClinicsRecruiting
- University of KentuckyRecruiting
- Norton Cancer InstituteRecruiting
- University Of Maryland Medical CenterRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- Barbara Ann Karmanos Cancer InstituteRecruiting
- Henry Ford Cancer InstituteRecruiting
- Columbia University Medical CenterRecruiting
- Memorial Sloan-Kettering Cancer CenterRecruiting
- New York Presbyterian-Weill Cornell Medical CollegeRecruiting
- Levine Cancer InstituteRecruiting
- Thomas Jefferson UniversityRecruiting
- University of Pittsburgh Medical CenterRecruiting
- University of VirginiaRecruiting
- Medical College Of WisconsinRecruiting
- Hospital AlemanRecruiting
- Hospital Italiano de Buenos AiresRecruiting
- Hospital Privado Centro Medico de CordobaRecruiting
- Royal Prince Alfred HospitalRecruiting
- St. Vincent's Hospital MelbourneRecruiting
- Austin HealthRecruiting
- Royal Brisbane and Womens HospitalRecruiting
- Alfred HealthRecruiting
- Peter MacCallum Cancer CentreRecruiting
- Fiona Stanley HospitalRecruiting
- Calvary Mater Newcastle HospitalRecruiting
- Western Sydney Local Health DistrictRecruiting
- Medizinische Universität Graz, LKH-Univ.Klinikum Graz, Klinische Abteilung für HämatologieRecruiting
- Krankenhaus der Elisabethinen LinzRecruiting
- LKH - Universitätsklinikum der PMU SalzburgRecruiting
- Medical University of Vienna,Universitätsklinik für Innere Medizin IRecruiting
- Universitair Ziekenhuis - AntwerpenRecruiting
- AZ St.-Jan Brugge-Oostende AVRecruiting
- UZ GentRecruiting
- UZ Leuven
- Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
- Hospital Sao RafaelRecruiting
- Fundacao Antonio Prudente - A.C. Camargo Cancer CenterRecruiting
- Sociedade Beneficente Israelita Brasileira Hospital Albert EinsteinRecruiting
- Tom Baker Cancer CentreRecruiting
- Vancouver General HospitalRecruiting
- Juravinski Cancer CentreRecruiting
- Princess Margaret Cancer Centre University Health NetworkRecruiting
- Hopital Maisonneuve-RosemontRecruiting
- Fakultni nemocnice BrnoRecruiting
- Fakultni nemocnice Hradec KraloveRecruiting
- Fakultni nemocnice OstravaRecruiting
- Vseobecna fakultni nemocnice v PrazeRecruiting
- Aarhus University HospitalRecruiting
- RigshospitaletRecruiting
- Odense UniversitetshospitalRecruiting
- Helsinki University HospitalRecruiting
- Oulu University HospitalRecruiting
- Turku University HospitalRecruiting
- Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude HuriezRecruiting
- C.H.U. Hotel Dieu - FranceRecruiting
- Hopital Saint-LouisRecruiting
- CHU Poitiers - Hôpital la MilétrieRecruiting
- Institut Universitaire du cancer de Toulouse-OncopoleRecruiting
- Charité - Universitätsmedizin Berlin, Campus Benjamin FranklinRecruiting
- Universitaetsklinikum Carl Gustav Carus TU DresdenRecruiting
- Universitatsklinikum FreiburgRecruiting
- Universitaetsklinikum Hamburg EppendorfRecruiting
- Universitaetsklinikum HeidelbergRecruiting
- Universitaetsklinikum LeipzigRecruiting
- Universitätsmedizin der Johannes Gutenberg-Universität MainzRecruiting
- Klinikum Großhadern der Ludwig-Maximilians-UniversitätRecruiting
- Universitaetsklinikum RegensburgRecruiting
- Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-GermanyRecruiting
- Universitätsklinikum WürzburgRecruiting
- Alexandra General Hospital of AthensRecruiting
- Attikon University General Hospital of AtticaRecruiting
- G.PapanikolaouRecruiting
- Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet, Szent László TelephelyRecruiting
- Debreceni Egyetem Klinikai KozpontRecruiting
- St James HospitalRecruiting
- Hadassah University Hospita - Ein KeremRecruiting
- Sheba Medical Center Tel HashomerRecruiting
- Tel Aviv Sourasky Medical CenterRecruiting
- Juntendo University HospitalRecruiting
- Kyushu University HospitalRecruiting
- Hyogo Medical University HospitalRecruiting
- Kanazawa University HospitalRecruiting
- University Hospital Kyoto Perfectural University of MedicineRecruiting
- Nagoya City University HospitalRecruiting
- Okayama University HospitalRecruiting
- Hokkaido University HospitalRecruiting
- Tohoku University HospitalRecruiting
- Japanese Red Cross Medical CenterRecruiting
- Chonnam National University Hwasun HospitalRecruiting
- Seoul National University HospitalRecruiting
- Severance Hospital, Yonsei University Health SystemRecruiting
- Asan Medical CenterRecruiting
- Samsung Medical CenterRecruiting
- The Catholic University of Korea Seoul St. Mary's HospitalRecruiting
- University Medical Center GroningenRecruiting
- UMC RadboudRecruiting
- Erasmus MCRecruiting
- Oslo universitetssykehus HF, RikshospitaletRecruiting
- Uniwersyteckie Centrum KliniczneRecruiting
- Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w GliwicachRecruiting
- Centrum Onkologii Ziemi Lubelskiej im. św. Jana z DukliRecruiting
- Uniwersytecki Szpital Kliniczny w PoznaniuRecruiting
- Instytut Hematologii i TransfuzjologiiRecruiting
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we WroclawiuRecruiting
- Instituto Portugues de OncologiaRecruiting
- Instituto Portugues de OncologiaRecruiting
- Hosp. de La Santa Creu I Sant PauRecruiting
- Hosp. Univ. Vall D HebronRecruiting
- Instituto Catalan Deoncologia Hospital Duran I ReynalsRecruiting
- Hosp. Gral. Univ. Gregorio MaranonRecruiting
- Hosp. Univ. 12 de OctubreRecruiting
- Hosp. Univ. Virgen de La ArrixacaRecruiting
- Clinica Univ. de NavarraRecruiting
- Hosp. Clinico Univ. de SalamancaRecruiting
- Hosp. Univ. Marques de ValdecillaRecruiting
- Hosp. Virgen Del RocioRecruiting
- Hosp. Univ. I Politecni La FeRecruiting
- Sahlgrenska University Hospital
- UniversitetssjukhusetRecruiting
- Skane University HospitalRecruiting
- Universitatsspital BaselRecruiting
- INSELSPITAL, Universitätsspital BernRecruiting
- Kantonsspital St.GallenRecruiting
- University Hospitals Birmingham NHS Trust,Recruiting
- Bristol Royal InfirmaryRecruiting
- Leeds Teaching Hospitals NHS TrustRecruiting
- University College HospitalRecruiting
- King's College HospitalRecruiting
- Manchester Royal InfirmaryRecruiting
- The Royal Marsden NHS Trust SuttonRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A: VRd+Rd (Standard Therapy)
Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)
Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity.
Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg).