A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma

Multiple Myeloma Clinical Trial

— CARTITUDE-6  

Official title:

A Phase 3 Randomized Study Comparing Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05257083
• Other study ID #: EMN28/68284528MMY3005
• Secondary ID: 2021-003284-10
• Status: Recruiting
• Phase: Phase 3
• Start date: October 10, 2023
• Est. completion date: August 2040

Study information

• Verified date: June 2024
• Source: Stichting European Myeloma Network
• Contact: Sarah Lonergan
• Phone: +31 107033123
• Email: sarah.lonergan[@]emn.life
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.

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) that is being evaluated to treat participants with multiple myeloma. The primary hypothesis is that in transplant-eligible participants with newly diagnosed multiple myeloma (NDMM), cilta-cel will significantly improve progression-free survival (PFS) and Sustained MRD-negative CR rate compared with Autologous Stem Cell Transplant (ASCT).

Approximately 750 participants (375 per arm) will be randomly assigned in a 1:1 ratio into 2 arms.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: August 2040
• Est. primary completion date: June 2033
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.

• Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:

1. Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or

2. Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) =10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.

• ECOG performance status of grade 0 or 1

• Clinical laboratory values within prespecified range.

Exclusion Criteria:

• Prior treatment with CAR-T therapy directed at any target.

• Any prior BCMA target therapy.

• Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids

• Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization

• Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.

• 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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Princess Alexandra Hospital	Brisbane
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Royal Brisbane and Womens Hospital	Herston
Australia	Alfred Health	Melbourne
Australia	Austin Hospital	Melbourne
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	St. Vincent's Hospital	Melbourne
Australia	Fiona Stanley Hospital	Murdoch
Australia	Calvary Mater Newcastle Hospital	Waratah
Australia	Westmead Hospital	Westmead
Belgium	UZA	Antwerpen
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Canada	Tom Baker Cancer Center	Calgary
Canada	Cross Cancer Institute	Edmonton
Canada	McMaster University	Hamilton
Canada	Hopital Maisonneuve-Rosemont	Montréal
Canada	Mcgill University Health Centre	Montréal
Canada	Ottawa Hospital Research Institute	Ottawa
Canada	(CHU) Centre Hospitalier Universitaire de Quebec Laval	Québec
Canada	Princess Margaret Cancer Centre	Toronto
Canada	Vancouver General Hospital	Vancouver
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Králová
Czechia	Fakutni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Plzen	Plzen
Czechia	Vseobecna fakultni nemocnice v Prague	Prague
France	CHRU de Lille - Hopital Claude Huriez	Lille
France	Hospices Civils De Lyon	Lyon
France	CHU De Nantes - Hématologie Clinique	Nantes
France	Aphp Direction	Paris
France	CHU Poitiers - Pôle régional de Cancérologie	Poitiers
France	Hopital Saint Louis - Aphp Hôpitaux Universitaires Saint-Louis	Saint-Louis
France	CHU de Toulouse	Toulouse
Germany	University Hospital of Cologne	Cologne
Germany	Dresden	Dresden
Germany	Universitätsklinikum Hamburg - Eppendorf	Hamburg
Germany	Nationales Centrum für Tumorerkrankungen (NCT) Abt. Medizinische Onkologie	Heidelberg
Germany	University Hospital of Leipzig	Leipzig
Germany	Tübingen	Tübingen
Germany	University Hospital of Würzburg	Würzburg
Greece	Attikon University General Hospital of Attica	Athens
Greece	'G. Papanikolaou' Hospital of Thessaloniki	Thessaloníki
Israel	Hadassah University Hospita - Ein Kerem	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi Di Ancona	Ancona
Italy	Policlinico S Orsola Malpighi	Bologna
Italy	A.O.U. Policlinico S. Martino - Ematologia	Genova
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano	Milan
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette, Turin	Turin
Japan	Juntendo University Hospital	Bunkyo-Ku
Japan	Kyushu University Hospital - Hematology/Oncology	Fukuoka
Japan	Hokkaido University Hospital-Department of Hematology	Hokkaido
Japan	Hyogo College of Medicine	Hyogo
Japan	Kanazawa University Hospital	Kanazawa
Japan	Nagoya City University Hospital - Department of Hematology & Oncology	Nagoya
Japan	Okayama University Hospital - Hematology/Oncology	Okayama
Japan	Osaka metropolitan university hospital	Osaka
Japan	Japanese Red Cross Medical Center - Hematology	Shibuya
Japan	Keio University Hospital - Hematology	Shinjuku-Ku
Japan	Tohoku University Hospital - Hematology	Tohoku
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Radboud UMC	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	UMC Utrecht	Utrecht
Norway	Oslo University Hospital Ullevål - Oncology	Oslo
Spain	Hospital Universitario Germans Trias i Pujol	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Instituto Catalán de Oncología	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	CLINICA UNIV. DE NAVARRA, Pamplona	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario la Fe, Valencia	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Landstinget i Ostergotland-Universitetssjukhuset i Linkoping	Linköping
Sweden	Skånes University Hospital Lund	Lund
Sweden	Akademiska Sjukhuset	Uppsala
Switzerland	Universitaetsspital Basel - Zentrum fur Hamato-Onkologie	Basel
Switzerland	Bern Inselspital	Bern
Switzerland	Lausanne CHUV Département d'oncologie	Lausanne
Switzerland	UniversitaetsSpital Zürich	Zürich
United Kingdom	Queen Elizabeth Medical Centre	Birmingham
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore M-E Center	Bronx	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke Cancer Institute	Durham	North Carolina
United States	University of Iowa	Iowa City	Iowa
United States	The University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Arkansas	Little Rock	Arkansas
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Medical College Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Venter	New York	New York
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Univ. of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania
United States	Mayo Clinic Hospital - Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	UC San Diego Health Moores Cancer Center	San Diego	California
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Stichting European Myeloma Network	Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Netherlands,  Norway,  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 PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first	up to 10 years ( or 300 PFS events)
Primary	Sustained MRD-negative CR	Sustained MRD-negative CR is defined as being MRD negative by bone marrow aspirate, as determined by NGS with a sensitivity of at least 10-5, and meeting the IMWG criteria for CR, and with MRD-negativity status confirmed at a minimum 12 months apart and without any examination showing MRD-positive status or PD in between.	up to 24 months
Secondary	Overall Response (OR)	OR is defined as participants who achieve a partial response (PR) or better according to the IMWG criteria.	up to 17 years
Secondary	Complete Response (CR) or better status	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 17 years
Secondary	Overall Minimal Residual Disease (MRD) -negative CR	achieving MRD-negative CR, as determined by NGS at any time after the date of randomization before initiation of subsequent antimyeloma therapy.	up to 17 years
Secondary	Time to subsequent antimyeloma therapy	Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy.	up to 17 years
Secondary	Progression Free Survival on Next-line Therapy (PFS2)	the time from the date of randomization to the date of event, defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death due to any cause, whichever occurs first.	up to 17 years
Secondary	Overall Survival (OS)	Overall survival is measured from the date of randomization to the date of the participant's death.	up to 17 years
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.	up to 17 years
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.	up to 17 years
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 Scor	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).	up to 17 years
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).	up to 17 years
Secondary	Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	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 280 days