Multiple Myeloma Clinical Trial
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
Summary
The purpose of this study is to compare the efficacy of Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by a single administration of ciltacabtagene autoleucel (cilta-cel) versus VRd induction followed by Lenalidomide and Dexamethasone (Rd) maintenance in newly diagnosed multiple myeloma participants for whom ASCT is not planned as initial therapy in terms of Progression Free Survival (PFS).
Full Description
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.
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)
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There are 134 Locations for this study
San Francisco California, 94143, United States
New Haven Connecticut, 06510, United States
Miami Florida, 33136, United States
Orlando Florida, 32832, United States
Iowa City Iowa, 52242, United States
Lexington Kentucky, 40536, United States
Louisville Kentucky, 40207, United States
Baltimore Maryland, 21201, United States
Boston Massachusetts, 02215, United States
Detroit Michigan, 48201, United States
Detroit Michigan, 48202, United States
New York New York, 10032, United States
New York New York, 10065, United States
New York New York, 10065, United States
Charlotte North Carolina, 28204, United States
Philadelphia Pennsylvania, 19107, United States
Pittsburgh Pennsylvania, 15232, United States
Charlottesville Virginia, 22903, United States
Milwaukee Wisconsin, 53226, United States
Buenos Aires , C1118, Argentina
Buenos Aires , C1199, Argentina
Cordoba , X5016, Argentina
Camperdown , 2050, Australia
Fitzroy , 3065, Australia
Heidelberg , 3084, Australia
Herston , 4029, Australia
Melbourne , 3004, Australia
Melbourne , 8006, Australia
Murdoch , 6150, Australia
Waratah , 2298, Australia
Westmead , 2145, Australia
Graz , 8036, Austria
Linz , 4020, Austria
Salzburg , 5020, Austria
Vienna , 1090, Austria
Antwerp , 2650, Belgium
Brugge , 8000, Belgium
Gent , 9000, Belgium
Leuven , 3000, Belgium
Liege , B-400, Belgium
Salvador , 41253, Brazil
Sao Paulo , 01509, Brazil
São Paulo , 05652, Brazil
Calgary Alberta, T2N 4, Canada
Vancouver British Columbia, V5Z 1, Canada
Hamilton Ontario, L8V5C, Canada
Toronto Ontario, M5G2M, Canada
Montréal Quebec, H1T 2, Canada
Brno , 625 0, Czechia
Hradec Kralove , 500 0, Czechia
Ostrava - Poruba , 708 5, Czechia
Praha 2 , 128 0, Czechia
Aarhus C , 8000, Denmark
Copenhagen , 2100, Denmark
Odense C , 5000, Denmark
Helsinki , 00029, Finland
Oulu , 90220, Finland
Turku , 20520, Finland
Lille Cedex , 59000, France
Nantes , 44093, France
Paris cedex 10 , 75475, France
Poitiers , 86021, France
Toulouse cedex 9 , 31059, France
Berlin , 12203, Germany
Dresden , 01307, Germany
Freiburg , 79106, Germany
Hamburg , 20246, Germany
Heidelberg , 69120, Germany
Leipzig , 04103, Germany
Mainz , 55131, Germany
München , 81377, Germany
Regensburg , 93053, Germany
Tubingen , 72076, Germany
Wuerzburg , 97080, Germany
Athens , 11528, Greece
Athens , 12462, Greece
Thessaloniki , 57010, Greece
Budapest , 1097, Hungary
Debrecen , 4032, Hungary
Dublin , D08 N, Ireland
Jerusalem , P.O.B, Israel
Ramat Gan , 52621, Israel
Tel Aviv , 64239, Israel
Bunkyo Ku , 113 8, Japan
Fukuoka , 812 8, Japan
Hyôgo , 663-8, Japan
Kanazawa , 920-8, Japan
Kyoto , 602-8, Japan
Nagoya , 467 8, Japan
Okayama , 700-8, Japan
Sapporo , 060-8, Japan
Sendai , 980 8, Japan
Shibuya , 150-8, Japan
Jeollanam-do , 58128, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 05505, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 06591, Korea, Republic of
Amsterdam , 1081 , Netherlands
Groningen , 9713 , Netherlands
Nijmegen , 6500 , Netherlands
Rotterdam , 3075 , Netherlands
Oslo , 0372, Norway
Gdansk , 80-21, Poland
Gliwice , 44102, Poland
Lublin , 20-09, Poland
Poznan , 60-56, Poland
Warszawa , 02-77, Poland
Wroclaw , 50-36, Poland
Lisboa , 1099-, Portugal
Porto , 42000, Portugal
Barcelona , 08025, Spain
Barcelona , 8035, Spain
L'Hospitalet de Llobregat , 08908, Spain
Madrid , 28007, Spain
Madrid , 28041, Spain
Murcia , 30120, Spain
Pamplona , 31008, Spain
Salamanca , 37007, Spain
Santander , 39008, Spain
Sevilla , 41013, Spain
Valencia , 46026, Spain
Goteborg , 413 4, Sweden
Linköping , 58185, Sweden
Lund , 221 8, Sweden
Basel , 4031, Switzerland
Bern , 3010, Switzerland
St. Gallen , 9007, Switzerland
Birmingham , B15 2, United Kingdom
Bristol , BS2 8, United Kingdom
Leeds, , LS9 7, United Kingdom
London , NW1 2, United Kingdom
London , SE5 9, United Kingdom
Manchester , M13 9, United Kingdom
Surrey , SM2 5, United Kingdom
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