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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04181827




Registration number
NCT04181827
Ethics application status
Date submitted
27/11/2019
Date registered
2/12/2019

Titles & IDs
Public title
A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma
Scientific title
A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Relapsed and Lenalidomide-Refractory Multiple Myeloma
Secondary ID [1] 0 0
2019-001413-16
Secondary ID [2] 0 0
CR108695
Universal Trial Number (UTN)
Trial acronym
CARTITUDE-4
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 - JNJ-68284528
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Daratumumab

Experimental: Arm A: PVd or DPd (Standard Therapy) - Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier.

Experimental: Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel]) - Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of JNJ-68284528 (cilta-cel) along with conditioning regimen (cyclophosphamide 300 milligram \[mg\]/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily, for 3 days), and JNJ-68284528 (cilta-cel) infusion 0.75 \* 10\^6 chimeric antigen receptor (CAR)-positive viable T cells/ kilogram (kg).


Treatment: Drugs: JNJ-68284528
Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).

Treatment: Drugs: Pomalidomide
Pomalidomide 4 mg will be administered orally.

Treatment: Drugs: Bortezomib
Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).

Treatment: Drugs: Dexamethasone
Dexamethasone 20 mg/day (10mg/day for participants \>75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants \>75 years of age) in DPd treatment.

Treatment: Drugs: Daratumumab
Daratumumab 1800 mg will be administered SC.

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
Until end of the study (up to 6 years)
Secondary outcome [1] 0 0
Complete Response (CR) or Stringent Complete Response (sCR) Rate
Timepoint [1] 0 0
Until end of the study (up to 6 years)
Secondary outcome [2] 0 0
Overall Minimal Residual Disease (MRD) Negative Rate
Timepoint [2] 0 0
Until end of the study (up to 6 years)
Secondary outcome [3] 0 0
MRD Negativity Rate in Participants with CR or sCR at 12 Months +/-3 Months
Timepoint [3] 0 0
Until end of the study (up to 6 years)
Secondary outcome [4] 0 0
Sustained MRD Negative Rate
Timepoint [4] 0 0
Until end of the study (up to 6 years)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Until end of the study (up to 6 years)
Secondary outcome [6] 0 0
Overall response rate (ORR)
Timepoint [6] 0 0
Until end of the study (up to 6 years)
Secondary outcome [7] 0 0
Time to Worsening of Symptoms
Timepoint [7] 0 0
Until end of the study (up to 6 years)
Secondary outcome [8] 0 0
Progression Free Survival on next-line therapy (PFS2)
Timepoint [8] 0 0
Until end of the study (up to 6 years)
Secondary outcome [9] 0 0
Incidence and Severity of Adverse Events (AEs)
Timepoint [9] 0 0
Until end of the study (up to 6 years)
Secondary outcome [10] 0 0
Systemic Cytokine Concentrations
Timepoint [10] 0 0
Until end of the study (up to 6 years)
Secondary outcome [11] 0 0
Levels of CAR-T Cell Activation Markers
Timepoint [11] 0 0
Until end of the study (up to 6 years)
Secondary outcome [12] 0 0
Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence
Timepoint [12] 0 0
Until end of the study (up to 6 years)
Secondary outcome [13] 0 0
Number of Participants with Anti-JNJ-68284528 Antibodies
Timepoint [13] 0 0
Until end of the study (up to 6 years)
Secondary outcome [14] 0 0
Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
Timepoint [14] 0 0
Until end of the study (up to 6 years)
Secondary outcome [15] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore
Timepoint [15] 0 0
Until end of the study (up to 6 years)
Secondary outcome [16] 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 [16] 0 0
Until end of the study (up to 6 years)
Secondary outcome [17] 0 0
Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
Timepoint [17] 0 0
Until end of the study (up to 6 years)
Secondary outcome [18] 0 0
Frequency in Health-Related Quality of Life as Assessed by The Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item
Timepoint [18] 0 0
Until end of the study (up to 6 years)

Eligibility
Key inclusion criteria
* Measurable disease at screening as defined by any of the following: (a) Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 0.5 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours; or (b) Light chain multiple myeloma without measurable M-protein in the serum or the urine: Serum free light chain >=10 mg/dL and abnormal serum free light chain ratio
* Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
* Have documented evidence of PD by International Myeloma Working Group (IMWG) criteria based on investigator's determination on or within 6 months of their last regimen
* Be refractory to lenalidomide per IMWG consensus guidelines (failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For participants with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy. However, participants must be refractory to lenalidomide in at least one prior line
* Have clinical laboratory values meeting the following criteria during the Screening Phase (re testing is allowed but the below criteria must be met in the latest test prior to randomization):

1. Hemoglobin >=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
2. Absolute neutrophil count (ANC) >=1 * 10^9 per liter (L) (without recombinant human granulocyte colony-stimulating factor [G-CSF] within 7 days and without pegylated G-CSF within 14 days of the laboratory test);
3. Platelet count >=75 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom less than (<) 50 percent (%) of bone marrow nucleated cells are plasma cells; platelet count >=50 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom >=50% of bone marrow nucleated cells are plasma cells;
4. Lymphocyte count >=0.3 * 10^9/L;
5. Aspartate aminotransferase (AST) less than or equal to (<=)3 * upper limit of normal (ULN);
6. Alanine aminotransferase (ALT) <=3 * ULN;
7. Total bilirubin <=2.0 * ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=1.5 * ULN is required);
8. Estimated glomerular filtration rate >=40 milliliter per minute (mL/min) per 1.73 meter square (m^2) (to be calculated using the Modification of Diet in Renal Disease [MDRD] formula)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy directed at any target
* Any previous therapy that is targeted to B-cell maturation antigen (BCMA)
* Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia
* Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive pomalidomide, bortezomib, and dexamethasone (PVd) as standard therapy or bridging therapy; however, participants may receive daratumumab, pomalidomide, and dexamethasone (DPd) as standard therapy or bridging therapy
* Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days prior to randomization
* Monoclonal antibody treatment within 21 days
* Cytotoxic therapy within 14 days
* Proteasome inhibitor therapy within 14 days
* Immunomodulatory drug (IMiD) therapy within 7 days

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
Active, not 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 Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Royal Brisbane and Womens Hospital - Herston
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Alfred Health - Melbourne
Recruitment hospital [6] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
Belgium
State/province [18] 0 0
Antwerp
Country [19] 0 0
Belgium
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Gent
Country [20] 0 0
Belgium
State/province [20] 0 0
Leuven
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Belgium
State/province [21] 0 0
Liege
Country [22] 0 0
Denmark
State/province [22] 0 0
Copenhagen
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France
State/province [23] 0 0
LILLE Cedex
Country [24] 0 0
France
State/province [24] 0 0
Montpellier
Country [25] 0 0
France
State/province [25] 0 0
Nantes
Country [26] 0 0
France
State/province [26] 0 0
Paris cedex 10
Country [27] 0 0
France
State/province [27] 0 0
Pierre Benite cedex
Country [28] 0 0
France
State/province [28] 0 0
Poitiers
Country [29] 0 0
France
State/province [29] 0 0
Toulouse cedex 9
Country [30] 0 0
Germany
State/province [30] 0 0
Dresden
Country [31] 0 0
Germany
State/province [31] 0 0
Hamburg
Country [32] 0 0
Germany
State/province [32] 0 0
Koeln
Country [33] 0 0
Germany
State/province [33] 0 0
Leipzig
Country [34] 0 0
Germany
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Tubingen
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Germany
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Wuerzburg
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Greece
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Athens
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Israel
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Jerusalem
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Israel
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Ramat Gan
Country [39] 0 0
Israel
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Tel Aviv
Country [40] 0 0
Italy
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Bologna
Country [41] 0 0
Italy
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Milano
Country [42] 0 0
Italy
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Roma
Country [43] 0 0
Italy
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Turin
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Japan
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Fukuoka
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Japan
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Kanazawa
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Japan
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Kyoto
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Japan
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Nagoya
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Japan
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Okayama
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Japan
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Sapporo
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Japan
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Sendai
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Japan
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Shibuya
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Groningen
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Netherlands
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Rotterdam
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Netherlands
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Utrecht
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Poland
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Gdansk
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Poland
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Gliwice
Country [59] 0 0
Poland
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Poznan
Country [60] 0 0
Poland
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Warszawa
Country [61] 0 0
Spain
State/province [61] 0 0
Badalona
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Spain
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Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Pamplona
Country [65] 0 0
Spain
State/province [65] 0 0
Salamanca
Country [66] 0 0
Spain
State/province [66] 0 0
Sevilla
Country [67] 0 0
Sweden
State/province [67] 0 0
Lund
Country [68] 0 0
Sweden
State/province [68] 0 0
Stockholm
Country [69] 0 0
Sweden
State/province [69] 0 0
Uppsala
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Birmingham
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Bristol
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Cardiff
Country [73] 0 0
United Kingdom
State/province [73] 0 0
London
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Manchester
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Newcastle Upon Tyne

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
Address 0 0
Country 0 0
Phone 0 0
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.