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

Multiple Myeloma Clinical Trial

— CARTITUDE-5  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04923893
• Other study ID #: CR109015
• Secondary ID: 2021-001242-3568
• Status: Recruiting
• Phase: Phase 3
• Start date: August 19, 2021
• Est. completion date: December 13, 2034

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 650
• Est. completion date: December 13, 2034
• Est. primary completion date: June 11, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib
Bortezomib will be administered SC.
• Dexamethasone
Dexamethasone will be administered orally.
• Lenalidomide
Lenalidomide will be administered orally.
• Cilta-cel
Cilta-cel infusion will be administered.
• Cyclophosphamide
Cyclophosphamide will be administered intravenously.
• Fludarabine
Fludarabine will be administered intravenously.

Locations

Country	Name	City	State
Argentina	Hospital Aleman	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	St. Vincent's Hospital Melbourne	Fitzroy
Australia	Austin Health	Heidelberg
Australia	Royal Brisbane and Womens Hospital	Herston
Australia	Alfred Health	Melbourne
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	Fiona Stanley Hospital	Murdoch
Australia	Calvary Mater Newcastle Hospital	Waratah
Australia	Western Sydney Local Health District	Westmead
Austria	Medizinische Universität Graz, LKH-Univ.Klinikum Graz, Klinische Abteilung für Hämatologie	Graz
Austria	Krankenhaus der Elisabethinen Linz	Linz
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Austria	Medical University of Vienna,Universitätsklinik für Innere Medizin I	Vienna
Belgium	Universitair Ziekenhuis - Antwerpen	Antwerp
Belgium	AZ St.-Jan Brugge-Oostende AV	Brugge
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman	Liege
Brazil	Hospital Sao Rafael	Salvador
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	São Paulo
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Hopital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Princess Margaret Cancer Centre University Health Network	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Denmark	Aarhus University Hospital	Aarhus C
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense Universitetshospital	Odense C
Finland	Helsinki University Hospital	Helsinki
Finland	Oulu University Hospital	Oulu
Finland	Turku University Hospital	Turku
France	Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez	Lille Cedex
France	C.H.U. Hotel Dieu - France	Nantes
France	Hopital Saint Louis	Paris cedex 10
France	CHU Poitiers - Hopital la Miletrie	Poitiers
France	Institut Universitaire du cancer de Toulouse-Oncopole	Toulouse cedex 9
Germany	Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	Universitaetsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Klinikum Großhadern der Ludwig-Maximilians-Universität	München
Germany	Universitaetsklinikum Regensburg	Regensburg
Germany	Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany	Tubingen
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Greece	Alexandra General Hospital of Athens	Athens
Greece	Attikon University General Hospital of Attica	Athens
Greece	G.Papanikolaou	Thessaloniki
Hungary	Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Ireland	St James Hospital	Dublin
Israel	Hadassah University Hospita - Ein Kerem	Jerusalem
Israel	Sheba Medical Center Tel Hashomer	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Japan	Juntendo University Hospital	Bunkyo Ku
Japan	Kyushu University Hospital	Fukuoka
Japan	Hyogo Medical University Hospital	Hyôgo
Japan	Kanazawa University Hospital	Kanazawa
Japan	University Hospital Kyoto Perfectural University of Medicine	Kyoto
Japan	Nagoya City University Hospital	Nagoya
Japan	Okayama University Hospital	Okayama
Japan	Hokkaido University Hospital	Sapporo
Japan	Tohoku University Hospital	Sendai
Japan	Japanese Red Cross Medical Center	Shibuya
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	UMC Radboud	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Norway	Oslo universitetssykehus HF, Rikshospitalet	Oslo
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach	Gliwice
Poland	Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli	Lublin
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Portugal	Instituto Portugues de Oncologia	Lisboa
Portugal	Instituto Portugues de Oncologia	Porto
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Instituto Catalan Deoncologia Hospital Duran I Reynals	L'Hospitalet de Llobregat
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Virgen de La Arrixaca	Murcia
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Sweden	Sahlgrenska University Hospital	Goteborg
Sweden	Universitetssjukhuset	Linköping
Sweden	Skane University Hospital	Lund
Switzerland	Universitatsspital Basel	Basel
Switzerland	INSELSPITAL Universitatsspital Bern	Bern
Switzerland	Kantonsspital St.Gallen	St. Gallen
United Kingdom	University Hospitals Birmingham NHS Trust,	Birmingham
United Kingdom	Bristol Royal Infirmary	Bristol
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds,
United Kingdom	King s College Hospital	London
United Kingdom	University College Hospital	London
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	The Royal Marsden NHS Trust Sutton	Surrey
United States	University Of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	University of Kentucky	Lexington	Kentucky
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Miami Health System	Miami	Florida
United States	Medical College Of Wisconsin	Milwaukee	Wisconsin
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York Presbyterian-Weill Cornell Medical College	New York	New York
United States	AdventHealth Cancer Institute	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	UCSF	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	Progression-free survival is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD), as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.	Up to 4 years and 5 months
Secondary	Sustained Minimal Residual Disease (MRD) Negative CR	Sustained MRD negative complete response (CR) as determined by next generation sequencing (NGS) with sensitivity of 10^-5, and defined by MRD negative CR plus at least 12 months durability of the MRD negative CR status.	Up to 12 years and 5 months
Secondary	MRD Negative CR at 9 Months	MRD negative CR rate at 9 months is defined as the percentage of participants who achieve MRD negative CR status at 9±3 months after the randomization date.	9 months
Secondary	Overall MRD Negative CR	Overall MRD negative is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy.	Up to 12 years and 5 months
Secondary	Overall Survival (OS)	Overall survival is measured from the date of randomization to the date of the participant's death.	Up to 12 years and 5 months
Secondary	Complete Response or Better	CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to the IMWG criteria.	Up to 12 years and 5 months
Secondary	Time to Subsequent Anti-myeloma Therapy	Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy.	Up to 12 years and 5 months
Secondary	Progression Free Survival on Next-line Therapy (PFS2)	PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.	Up to 12 years and 5 months
Secondary	Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs	Number of participants with AEs, abnormalities in laboratory parameters (complete blood count [CBC] with differential, coagulation, chimeric antigen receptor T cell [CAR-T] chemistry, full metabolic panel etc.), 12-lead ECG, physical examination, and vital signs will be reported.	Up to 12 years and 5 months
Secondary	Arm B: Systemic Cytokine Concentrations	Serum or plasma proteomic profiling of cytokines (such as interleukin [IL] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment.	Up to Day 112
Secondary	Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers	CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry, cytometry by time of flight (CyTOF), single cell RNA sequencing (scRNAseq) or similar technologies and be correlated with response.	Up to 12 years and 5 months
Secondary	Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA)	Levels of soluble BCMA will be reported.	Up to 1 year
Secondary	Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence	Levels of cilta-cel expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.	Up to 12 years and 5 months
Secondary	Arm B: Number of Participants with Anti-cilta-cel Antibodies	Number of participants with anti-cilta-cel antibodies will be reported.	Up to 12 years and 5 months
Secondary	Arm B: Number of Participants with Presence of Replication Competent Lentivirus	Number of participants with presence of replication competent lentivirus will be reported.	Up to 12 years and 5 months
Secondary	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	The EORTC QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Baseline up to 12 years and 5 months
Secondary	Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score	The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact.	Baseline up to 12 years and 5 months
Secondary	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	The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems, where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems, plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline up to 12 years and 5 months
Secondary	Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score	The PGIS uses 2 items to assess the participant's perception of the severity of their disease symptoms and impact using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).	Baseline up to 12 years and 5 months
Secondary	Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items	The National Cancer Institute's PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference that ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.	Up to 161 days
Secondary	Time to Worsening of Symptoms, Functioning and Overall Well-being	Time to worsening is measured as the interval from the date of randomization to the start date of worsening in MySIm-Q symptom, impact, or total scores.	Up to 12 year and 5 months

External Links

•   Click here to learn more about the 68284528MMY3004 (CARTITUDE-5) trial (US only)