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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04923893




Registration number
NCT04923893
Ethics application status
Date submitted
10/06/2021
Date registered
11/06/2021

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2021-001242-35
Secondary ID [2] 0 0
CR109015
Universal Trial Number (UTN)
Trial acronym
CARTITUDE-5
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Cilta-cel
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Fludarabine

Experimental: Arm A: VRd+Rd (Standard Therapy) - 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.

Experimental: Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) - 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).


Treatment: Drugs: Bortezomib
Bortezomib will be administered SC.

Treatment: Drugs: Dexamethasone
Dexamethasone will be administered orally.

Treatment: Drugs: Lenalidomide
Lenalidomide will be administered orally.

Treatment: Drugs: Cilta-cel
Cilta-cel infusion will be administered.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered intravenously.

Treatment: Drugs: Fludarabine
Fludarabine will be administered intravenously.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Up to 4 years and 5 months
Secondary outcome [1] 0 0
Sustained Minimal Residual Disease (MRD) Negative CR
Timepoint [1] 0 0
Up to 12 years and 5 months
Secondary outcome [2] 0 0
MRD Negative CR at 9 Months
Timepoint [2] 0 0
9 months
Secondary outcome [3] 0 0
Overall MRD Negative CR
Timepoint [3] 0 0
Up to 12 years and 5 months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Up to 12 years and 5 months
Secondary outcome [5] 0 0
Complete Response or Better
Timepoint [5] 0 0
Up to 12 years and 5 months
Secondary outcome [6] 0 0
Time to Subsequent Anti-myeloma Therapy
Timepoint [6] 0 0
Up to 12 years and 5 months
Secondary outcome [7] 0 0
Progression Free Survival on Next-line Therapy (PFS2)
Timepoint [7] 0 0
Up to 12 years and 5 months
Secondary outcome [8] 0 0
Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs
Timepoint [8] 0 0
Up to 12 years and 5 months
Secondary outcome [9] 0 0
Arm B: Systemic Cytokine Concentrations
Timepoint [9] 0 0
Up to Day 112
Secondary outcome [10] 0 0
Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers
Timepoint [10] 0 0
Up to 12 years and 5 months
Secondary outcome [11] 0 0
Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA)
Timepoint [11] 0 0
Up to 1 year
Secondary outcome [12] 0 0
Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence
Timepoint [12] 0 0
Up to 12 years and 5 months
Secondary outcome [13] 0 0
Arm B: Number of Participants with Anti-cilta-cel Antibodies
Timepoint [13] 0 0
Up to 12 years and 5 months
Secondary outcome [14] 0 0
Arm B: Number of Participants with Presence of Replication Competent Lentivirus
Timepoint [14] 0 0
Up to 12 years and 5 months
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Baseline up to 12 years and 5 months
Secondary outcome [16] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score
Timepoint [16] 0 0
Baseline up to 12 years and 5 months
Secondary outcome [17] 0 0
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
Timepoint [17] 0 0
Baseline up to 12 years and 5 months
Secondary outcome [18] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
Timepoint [18] 0 0
Baseline up to 12 years and 5 months
Secondary outcome [19] 0 0
Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items
Timepoint [19] 0 0
Up to 161 days
Secondary outcome [20] 0 0
Time to Worsening of Symptoms, Functioning and Overall Well-being
Timepoint [20] 0 0
Up to 12 year and 5 months

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Royal Brisbane and Womens Hospital - Herston
Recruitment hospital [5] 0 0
Alfred Health - Melbourne
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [7] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [8] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [9] 0 0
Western Sydney Local Health District - Westmead
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
8006 - Melbourne
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment postcode(s) [8] 0 0
2298 - Waratah
Recruitment postcode(s) [9] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Cordoba
Country [16] 0 0
Austria
State/province [16] 0 0
Graz
Country [17] 0 0
Austria
State/province [17] 0 0
Linz
Country [18] 0 0
Austria
State/province [18] 0 0
Salzburg
Country [19] 0 0
Austria
State/province [19] 0 0
Vienna
Country [20] 0 0
Belgium
State/province [20] 0 0
Antwerp
Country [21] 0 0
Belgium
State/province [21] 0 0
Brugge
Country [22] 0 0
Belgium
State/province [22] 0 0
Gent
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Liege
Country [25] 0 0
Brazil
State/province [25] 0 0
Salvador
Country [26] 0 0
Brazil
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Sao Paulo
Country [27] 0 0
Brazil
State/province [27] 0 0
São Paulo
Country [28] 0 0
Canada
State/province [28] 0 0
Alberta
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Czechia
State/province [32] 0 0
Brno
Country [33] 0 0
Czechia
State/province [33] 0 0
Hradec Kralove
Country [34] 0 0
Czechia
State/province [34] 0 0
Ostrava - Poruba
Country [35] 0 0
Czechia
State/province [35] 0 0
Praha 2
Country [36] 0 0
Denmark
State/province [36] 0 0
Aarhus C
Country [37] 0 0
Denmark
State/province [37] 0 0
Copenhagen
Country [38] 0 0
Denmark
State/province [38] 0 0
Odense C
Country [39] 0 0
Finland
State/province [39] 0 0
Helsinki
Country [40] 0 0
Finland
State/province [40] 0 0
Oulu
Country [41] 0 0
Finland
State/province [41] 0 0
Turku
Country [42] 0 0
France
State/province [42] 0 0
Lille Cedex
Country [43] 0 0
France
State/province [43] 0 0
Nantes
Country [44] 0 0
France
State/province [44] 0 0
Paris cedex 10
Country [45] 0 0
France
State/province [45] 0 0
Poitiers
Country [46] 0 0
France
State/province [46] 0 0
Toulouse cedex 9
Country [47] 0 0
Germany
State/province [47] 0 0
Berlin
Country [48] 0 0
Germany
State/province [48] 0 0
Dresden
Country [49] 0 0
Germany
State/province [49] 0 0
Freiburg
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Germany
State/province [50] 0 0
Hamburg
Country [51] 0 0
Germany
State/province [51] 0 0
Heidelberg
Country [52] 0 0
Germany
State/province [52] 0 0
Leipzig
Country [53] 0 0
Germany
State/province [53] 0 0
Mainz
Country [54] 0 0
Germany
State/province [54] 0 0
München
Country [55] 0 0
Germany
State/province [55] 0 0
Regensburg
Country [56] 0 0
Germany
State/province [56] 0 0
Tubingen
Country [57] 0 0
Germany
State/province [57] 0 0
Wuerzburg
Country [58] 0 0
Greece
State/province [58] 0 0
Athens
Country [59] 0 0
Greece
State/province [59] 0 0
Thessaloniki
Country [60] 0 0
Hungary
State/province [60] 0 0
Budapest
Country [61] 0 0
Hungary
State/province [61] 0 0
Debrecen
Country [62] 0 0
Ireland
State/province [62] 0 0
Dublin
Country [63] 0 0
Israel
State/province [63] 0 0
Jerusalem
Country [64] 0 0
Israel
State/province [64] 0 0
Ramat Gan
Country [65] 0 0
Israel
State/province [65] 0 0
Tel Aviv
Country [66] 0 0
Japan
State/province [66] 0 0
Bunkyo Ku
Country [67] 0 0
Japan
State/province [67] 0 0
Fukuoka
Country [68] 0 0
Japan
State/province [68] 0 0
Hyôgo
Country [69] 0 0
Japan
State/province [69] 0 0
Kanazawa
Country [70] 0 0
Japan
State/province [70] 0 0
Kyoto
Country [71] 0 0
Japan
State/province [71] 0 0
Nagoya
Country [72] 0 0
Japan
State/province [72] 0 0
Okayama
Country [73] 0 0
Japan
State/province [73] 0 0
Sapporo
Country [74] 0 0
Japan
State/province [74] 0 0
Sendai
Country [75] 0 0
Japan
State/province [75] 0 0
Shibuya
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Jeollanam-do
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Seoul
Country [78] 0 0
Netherlands
State/province [78] 0 0
Amsterdam
Country [79] 0 0
Netherlands
State/province [79] 0 0
Groningen
Country [80] 0 0
Netherlands
State/province [80] 0 0
Nijmegen
Country [81] 0 0
Netherlands
State/province [81] 0 0
Rotterdam
Country [82] 0 0
Norway
State/province [82] 0 0
Oslo
Country [83] 0 0
Poland
State/province [83] 0 0
Gdansk
Country [84] 0 0
Poland
State/province [84] 0 0
Gliwice
Country [85] 0 0
Poland
State/province [85] 0 0
Lublin
Country [86] 0 0
Poland
State/province [86] 0 0
Poznan
Country [87] 0 0
Poland
State/province [87] 0 0
Warszawa
Country [88] 0 0
Poland
State/province [88] 0 0
Wroclaw
Country [89] 0 0
Portugal
State/province [89] 0 0
Lisboa
Country [90] 0 0
Portugal
State/province [90] 0 0
Porto
Country [91] 0 0
Spain
State/province [91] 0 0
Barcelona
Country [92] 0 0
Spain
State/province [92] 0 0
L'Hospitalet de Llobregat
Country [93] 0 0
Spain
State/province [93] 0 0
Madrid
Country [94] 0 0
Spain
State/province [94] 0 0
Murcia
Country [95] 0 0
Spain
State/province [95] 0 0
Pamplona
Country [96] 0 0
Spain
State/province [96] 0 0
Salamanca
Country [97] 0 0
Spain
State/province [97] 0 0
Santander
Country [98] 0 0
Spain
State/province [98] 0 0
Sevilla
Country [99] 0 0
Spain
State/province [99] 0 0
Valencia
Country [100] 0 0
Sweden
State/province [100] 0 0
Goteborg
Country [101] 0 0
Sweden
State/province [101] 0 0
Linköping
Country [102] 0 0
Sweden
State/province [102] 0 0
Lund
Country [103] 0 0
Switzerland
State/province [103] 0 0
Basel
Country [104] 0 0
Switzerland
State/province [104] 0 0
Bern
Country [105] 0 0
Switzerland
State/province [105] 0 0
St. Gallen
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Birmingham
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Bristol
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Leeds,
Country [109] 0 0
United Kingdom
State/province [109] 0 0
London
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Manchester
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.