CARTITUDE-4: 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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04181827
Collaborator
(none)
400
Enrollment
100
Locations
2
Arms
69.9
Anticipated Duration (Months)
4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) with standard therapy, either Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd).

Detailed Description

Multiple myeloma is a malignant plasma cell disorder diagnosed annually in approximately 86,000 participants worldwide. JNJ-68284528 (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 for this study is that JNJ-68284528 (cilta-cel) will significantly improve progression free survival (PFS) compared with standard therapy (PVd or DPd), in participants who have previously received 1 to 3 prior line(s) of therapy, that included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who are refractory to lenalidomide. This study will be conducted in 3 phases: Screening (up to 28 days before randomization), Treatment, and Follow-Up. Assessment like patient-reported outcome(s) (PROs) assessments, electrocardiogram (ECG), vital signs, pharmacokinetic will be performed during the study. Safety evaluations will include review of adverse events, laboratory test results, vital sign measurements, physical examination findings, and assessments of cardiac function, Immune Effector Cell-associated Encephalopathy (only for Arm B) and Eastern Cooperative Oncology Group performance status. Safety data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 6 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official 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
Actual Study Start Date :
Jun 12, 2020
Anticipated Primary Completion Date :
Apr 10, 2026
Anticipated Study Completion Date :
Apr 10, 2026

Arms and Interventions

ArmIntervention/Treatment
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.

Drug: Pomalidomide
Pomalidomide 4 mg will be administered orally.

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

Drug: 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.

Drug: Daratumumab
Daratumumab 1800 mg will be administered SC.

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).

Drug: JNJ-68284528
Cilta-cel infusion will be administered at a target dose of 0.75 * 10^6 CAR-positive viable T cells/kilogram (kg).
Other Names:
  • Cilta-cel
  • Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [Until end of the study (up to 6 years)]

      PFS is defined as the time from the date of randomization to the date of first documented disease progression as defined in the IMWG criteria, or death due to any cause, whichever occurs first.

    Secondary Outcome Measures

    1. Complete Response (CR) or Stringent Complete Response (sCR) Rate [Until end of the study (up to 6 years)]

      CR or sCR rate is defined as percentage of participants who achieve a CR or sCR response according to the International Myeloma Working Group (IMWG) criteria.

    2. Overall Minimal Residual Disease (MRD) Negative Rate [Until end of the study (up to 6 years)]

      Overall MRD negativity is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy.

    3. MRD Negativity Rate in Participants with CR or sCR at 12 Months +/-3 Months [Until end of the study (up to 6 years)]

      MRD negativity rate in participants with CR or sCR at 12 months +/-3 months is defined as the percentage of participants who achieve MRD-negative status and are in CR or sCR within time window.

    4. Sustained MRD Negative Rate [Until end of the study (up to 6 years)]

      Sustained MRD negativity rate is defined as the percentage of participants who achieve MRD negativity, confirmed minimum 1 year apart and without any examination showing MRD positive status in between.

    5. Overall Survival (OS) [Until end of the study (up to 6 years)]

      OS is measured from the date of randomization to the date of the participant's death. If the participant is alive or the vital status is unknown, then the participant's data will be censored at the date the participant was last known to be alive.

    6. Overall response rate (ORR) [Until end of the study (up to 6 years)]

      ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.

    7. Time to Worsening of Symptoms [Until end of the study (up to 6 years)]

      Time to worsening of symptoms is measured as the interval from the date of randomization to the start date of worsening in the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) total symptom score. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days" and responses are reported on a 5 point verbal rating scale.

    8. Progression Free Survival on next-line therapy (PFS2) [Until end of the study (up to 6 years)]

      PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.

    9. Incidence and Severity of Adverse Events (AEs) [Until end of the study (up to 6 years)]

      Incidence and severity of AEs will be reported.

    10. Systemic Cytokine Concentrations [Until end of the study (up to 6 years)]

      Serum or plasma proteomic profiling of cytokines (such as interleukin [IL] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment.

    11. Levels of CAR-T Cell Activation Markers [Until end of the study (up to 6 years)]

      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 or cytometry by time of flight (CyTOF) or both and correlated with response.

    12. Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [Until end of the study (up to 6 years)]

      Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.

    13. Number of Participants with Anti-JNJ-68284528 Antibodies [Until end of the study (up to 6 years)]

      Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.

    14. 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 [Until end of the study (up to 6 years)]

      The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. 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.

    15. Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore [Until end of the study (up to 6 years)]

      The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days" and responses are reported on a 5 point verbal rating scale.

    16. 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 [Until end of the study (up to 6 years)]

      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 plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

    17. Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score [Until end of the study (up to 6 years)]

      The PGIS is a single item to assess the participant's perception in the severity of their overall health status using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).

    18. 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 [Until end of the study (up to 6 years)]

      Frequency distributions of the 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 of the adverse event. A 5-point verbal rating scale is used for participants to select their experience based on the last 7 days.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 * 109/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 * 109/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)

    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35294
    2Mayo Clinic Cancer Center-ScottsdalePhoenixArizonaUnited States85054
    3Stanford University Medical CenterStanfordCaliforniaUnited States94305-5623
    4Colorado Blood Cancer InstituteDenverColoradoUnited States80218
    5Yale New Haven HospitalNew HavenConnecticutUnited States06520
    6University of Miami Leonard M. Miller School of Medicine - Sylvester Comprehensive Cancer CenterMiamiFloridaUnited States33136-1002
    7Emory UniversityAtlantaGeorgiaUnited States30322
    8Northside Hospital Cancer InstituteAtlantaGeorgiaUnited States30342
    9University of Iowa Hospitals & ClinicsIowa CityIowaUnited States52242
    10University of KansasWestwoodKansasUnited States66205
    11University Of Maryland Medical CenterBaltimoreMarylandUnited States21201
    12University of Michigan Health SystemAnn ArborMichiganUnited States48109
    13University Of MinnesotaMinneapolisMinnesotaUnited States55455
    14Mayo Clinic - RochesterRochesterMinnesotaUnited States55905
    15Washington University School of MedicineSaint LouisMissouriUnited States63110
    16Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    17Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10065
    18University of Rochester Medical CenterRochesterNew YorkUnited States14642
    19Duke University Medical CenterDurhamNorth CarolinaUnited States27710
    20Cleveland ClinicClevelandOhioUnited States44195
    21The Ohio State UniversityColumbusOhioUnited States43210
    22Sarah Cannon Research InstituteNashvilleTennesseeUnited States37203
    23Huntsman Cancer InstituteSalt Lake CityUtahUnited States84112
    24University of Wisconsin Carbone Cancer CenterMadisonWisconsinUnited States53792
    25Medical College Of WisconsinMilwaukeeWisconsinUnited States53226
    26Royal Adelaide HospitalAdelaideAustralia5000
    27Royal Prince Alfred HospitalCamperdownAustralia2050
    28Royal Brisbane and Womens HospitalHerstonAustralia4029
    29Alfred HealthMelbourneAustralia3004
    30Peter MacCallum Cancer CentreMelbourneAustralia8006
    31Fiona Stanley HospitalMurdochAustralia6150
    32Calvary Mater Newcastle HospitalWaratahAustralia2298
    33Western Sydney Local Health DistrictWestmeadAustralia2145
    34Universitair Ziekenhuis - AntwerpenAntwerpBelgium2650
    35Institut Jules BordetBrusselBelgium1000
    36UZ GentGentBelgium9000
    37UZ LeuvenLeuvenBelgium3000
    38Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart TilmanLiegeBelgiumB-4000
    39RigshospitaletCopenhagenDenmark2100
    40CHRU de Lille - Hôpital Claude HuriezLILLE CedexFrance59037
    41CHU de Montpellier, Hopital Saint-EloiMontpellierFrance34295
    42C.H.U. Hotel Dieu - FranceNantesFrance44093
    43Hopital Saint-LouisParis cedex 10France75475
    44CHU de Bordeaux - Hôpital Haut-LévêquePessac cedexFrance33604
    45Centre hospitalier Lyon-SudPierre Benite cedexFrance69495
    46CHU De PoitiersPoitiersFrance86021
    47Institut Universitaire du cancer de Toulouse-OncopoleToulouse cedex 9France31059
    48Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat DresdenDresdenGermany01307
    49Universitaetsklinikum Hamburg EppendorfHamburgGermany20246
    50Universitaetsklinikum HeidelbergHeidelbergGermany69120
    51Universitaetsklinikum KoelnKölnGermany50924
    52Universitatsklinikum LeipzigLeipzigGermany04103
    53Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-GermanyTübingenGermany72076
    54Universitätsklinikum WürzburgWürzburgGermany97080
    55Attikon University General Hospital of AtticaAthensGreece12462
    56'G. Papanikolaou' Hospital of ThessalonikiThessalonikisGreece570 10
    57Hadassah University Hospita - Ein KeremJerusalemIsraelP.O.B. 12000
    58Sheba Medical CenterRamat GanIsrael74047
    59Sourasky Medical CenterTel-AvivIsrael64239
    60Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di BolognaBolognaItaly40138
    61Ospedale San Raffaele HSR Istituto Scientifico Universitario San RaffaeleMilanoItaly20132
    62Fondazione IRCCS Istituto Nazionale dei TumoriMilanoItaly20133
    63Policlinico Universitario Agostino GemelliRomaItaly00168
    64A.O.U. Citta della Salute e della Scienza di Torino - Presidio MolinetteTurinItaly10126
    65Kyushu University HospitalFukuokaJapan812-8582
    66Kanazawa University HospitalKanazawaJapan920-8641
    67University Hospital Kyoto Perfectural University of MedicineKyotoJapan602-8566
    68Nagoya City University HospitalNagoyaJapan467-8602
    69Okayama University HospitalOkayamaJapan700-8558
    70Hokkaido University HospitalSapporoJapan060-8648
    71Tohoku University HospitalSendaiJapan980-8574
    72Japanese Red Cross Medical CenterShibuyaJapan150-8935
    73Samsung Medical CenterSeoulKorea, Republic of06351
    74The Catholic University of Korea, Seoul St. Mary's HospitalSeoulKorea, Republic of06591
    75Seoul National University HospitalSeoulKorea, Republic of3080
    76VU Medisch CentrumAmsterdamNetherlands1081 HV
    77University Medical Center GroningenGroningenNetherlands9713 GZ
    78Erasmus MCRotterdamNetherlands3015 CN
    79UMC UtrechtUtrechtNetherlands3584 CX
    80Uniwersyteckie Centrum KliniczneGdanskPoland80-952
    81Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w GliwicachGliwicePoland44102
    82Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola MarcinkowskiegoPoznanPoland60-569
    83Instytut Hematologii i TransfuzjologiiWarszawaPoland02-776
    84Inst. Cat. D'Oncologia-BadalonaBadalonaSpain08916
    85Hosp. Clinic I Provincial de BarcelonaBarcelonaSpain08036
    86Hosp. Gral. Univ. Gregorio MarañonMadridSpain28007
    87Hosp. Univ. 12 de OctubreMadridSpain28041
    88Clinica Univ. de NavarraPamplonaSpain31008
    89Hosp. Clinico Univ. de SalamancaSalamancaSpain37007
    90Hosp. Virgen Del RocioSevillaSpain41013
    91Skane University HospitalLundSweden221 85
    92Karolinska Universitetssjukhuset Huddinge, Hematologiska Kliniken, HuddingeStockholmSweden141 86
    93Akademiska SjukhusetUppsalaSweden751 85
    94Queen Elizabeth HospitalBirminghamUnited KingdomB15 2TH
    95Bristol Royal InfirmaryBristolUnited KingdomBS2 8BJ
    96University Hospital WalesCardiffUnited KingdomCF14 4XW
    97University College HospitalLondonUnited KingdomNW1 2BU
    98King's College HospitalLondonUnited KingdomSE5 9RS
    99Christie HospitalManchesterUnited KingdomM20 4BX
    100Freeman HospitalNewcastle Upon TyneUnited KingdomNE7 7DN

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT04181827
    Other Study ID Numbers:
    • CR108695
    • 2019-001413-16
    • 68284528MMY3002
    First Posted:
    Dec 2, 2019
    Last Update Posted:
    Nov 5, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 5, 2021