CARTITUDE-2: A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04133636
Collaborator
(none)
160
Enrollment
42
Locations
1
Arm
69.1
Anticipated Duration (Months)
3.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.

Detailed Description

Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. The main aim of the study is to determine the safety and efficacy of JNJ-68284528 in various clinical settings. JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA). The study comprises of a Screening Phase (less than or equal to [<=] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment); a Treatment Phase including a conditioning regimen followed by infusion of JNJ-68284528 and post-infusion assessments from Day 1 to Day 100 (participants who receive an infusion of JNJ-68284528 should continue all subsequent assessments); and a Post-treatment Phase (Day 101 and up to the end of each study cohort). Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, physical examination findings (including neurologic examination), assessment of cardiac function, immune effector cell-associated encephalopathy (ICE) score, handwriting assessment, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade. Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. For certain participants (those without measurable disease in serum or urine) efficacy will be assessed via imaging: positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI). The overall duration of the study is up to 2.5 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
160 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma
Actual Study Start Date :
Nov 7, 2019
Anticipated Primary Completion Date :
May 2, 2022
Anticipated Study Completion Date :
Aug 9, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: JNJ-68284528

Single group assignment-After lymphodepletion, JNJ-68284528 will be administered as single infusion to participants in cohort A (Progressive disease after 1-3 prior lines of therapy), cohort B (Early relapse after front-line), cohort C (Relapsed/refractory multiple myeloma after PI, IMiD, anti-CD38, and anti- BCMA therapy), cohort D (Less than CR after ASCT front-line therapy; some participants will be administered JNJ-68284528 followed by lenalidomide), cohort F (Newly diagnosed multiple myeloma [NDMM] with standard risk [international staging system {ISS} Stage I and II] and after initiation of therapy). Participants in cohort E (NDMM, transplant not planned, high risk disease) will first be administered with quadruplet induction regimen of daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd), followed by lymphodepletion and JNJ-68284528, followed by consolidation regimen of daratumumab and lenalidomide (D+R).

Drug: JNJ-68284528
Participants in cohort A,B,C, D, E and F will receive JNJ-68284528 intravenously.
Other Names:
  • Ciltacabtagene autoleucel (cilta-cel)
  • Drug: Lenalidomide
    Some participants in cohort D and all participants in cohort E will also receive lenalidomide capsules orally.

    Drug: Daratumumab
    Participants in cohort E will also receive daratumumab subcutaneous (SC) injection.

    Drug: Bortezomib
    Participants in cohort E will also receive bortezomib subcutaneously.

    Drug: Dexamethasone
    Participants in cohort E will also receive dexamethasone orally or intravenously.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants with Negative Minimal Residual Disease (MRD) [At least 1 year after JNJ-68284528 infusion on Day 1]

      MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate as defined by the International Myeloma Working Group (IMWG) criteria.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 2 years and 6 months]

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

    2. VGPR or Better Rate [Up to 2 years and 6 months]

      The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment.

    3. Clinical Benefit Rate (CBR) [Up to 2 years and 6 months]

      CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.

    4. Duration of Response (DOR) [Up to 2 years and 6 months]

      DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria.

    5. Time to Response (TTR) [Up to 2 years and 6 months]

      TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.

    6. MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) [12 months]

      MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528.

    7. Time to MRD Negativity [Up to 2 years and 6 months]

      Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status.

    8. Duration of MRD Negativity [Up to 2 years and 6 months]

      Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5).

    9. MRD Negative Rate Across Clinical Response [Up to 2 years and 6 months]

      MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint.

    10. Number of Participants with Adverse Events by Severity [Up to 2 years and 6 months]

      An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.

    11. Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability [Up to 2 years and 6 months]

      An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    12. Number of Participants with Laboratory Abnormalities [Up to 2 years and 6 months]

      Number of participants with laboratory abnormalities will be reported.

    13. Number of Participants with Vital Sign Abnormalities [Up to 2 years and 6 months]

      Number of participants with vital sign abnormalities will be reported.

    14. Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [Up to 1 year]

      Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported.

    15. Systemic Inflammatory Cytokine Concentrations [Up to 1 year]

      Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.

    16. Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [Up to 1 year]

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

    17. Number of Participants with Anti-JNJ-68284528 Antibodies [Up to 1 year]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide refractory per International Myeloma Working Group (IMWG) guidelines

    • Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease progression per IMWG criteria less than or equal to (<=) 12 months after treatment with autologous stem cell transplantation (ASCT) or <=12 months from the start of anti-myeloma therapy for participants who have not had an ASCT

    • Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and B-cell maturation antigen (BCMA)-directed therapy

    • Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation

    • Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of prior therapy before enrollment is acceptable) and classified as high risk defined as either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin greater than or equal to (>=) 5.5 milligram per liter (mg/L) (via local or central laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 copies)

    Cohorts A, B, C, E:
    • 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

    • Light chain multiple myeloma in whom only measurable disease is by serum free light chain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio

    • Cohort A: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)*1 cm is required

    • Cohorts B, C: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria

    • Cohorts A, B, C, D, E, F: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

    • Cohort F: Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed per IMWG 2016 criteria

    Exclusion Criteria:
    • Cohorts A, B, D, F: Any therapy that is targeted to BCMA

    • Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target

    Cohorts A, B, C, D, F:
    • Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy

    • Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis

    • Serious underlying medical condition, such as (a) evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection; (b) active autoimmune disease or a history of autoimmune disease within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d) any history of Parkinson's disease or other neurodegenerative disorder

    • Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of California, San FranciscoSan FranciscoCaliforniaUnited States94143
    2Moffitt Cancer CenterTampaFloridaUnited States33612
    3Emory UniversityAtlantaGeorgiaUnited States30322
    4Northwestern UniversityChicagoIllinoisUnited States60611
    5University of ChicagoChicagoIllinoisUnited States60637
    6Indiana UniversityIndianapolisIndianaUnited States46202
    7Johns HopkinsBaltimoreMarylandUnited States21287
    8Dana-Farber Cancer InstituteBostonMassachusettsUnited States02115
    9Mayo Clinic RochesterRochesterMinnesotaUnited States55905
    10Washington University School of MedicineSaint LouisMissouriUnited States63110
    11Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    12Rutgers Cancer Institute of New JerseyNew BrunswickNew JerseyUnited States08903
    13Montefiore Medical CenterBronxNew YorkUnited States10467
    14Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263
    15Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
    16Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10065
    17Levine Cancer Institute, Carolinas HealthCare SystemCharlotteNorth CarolinaUnited States28204
    18University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
    19University of PittsburghPittsburghPennsylvaniaUnited States15232
    20Baylor University Medical CenterDallasTexasUnited States75246
    21University of Texas, MD Anderson Cancer CenterHoustonTexasUnited States77030
    22Fred Hutchinson Cancer CenterSeattleWashingtonUnited States98109
    23Universitair Ziekenhuis - AntwerpenAntwerpBelgium2650
    24Institut Jules BordetBrusselBelgium1000
    25UZ GentGentBelgium9000
    26UZ LeuvenLeuvenBelgium3000
    27CHRU de Lille - Hôpital Claude HuriezLilleFrance59000
    28C.H.U. Hotel Dieu - FranceNantesFrance44093
    29Hopital Saint-LouisParis cedex 10France75475
    30Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat DresdenDresdenGermany01307
    31Universitaetsklinikum Hamburg EppendorfHamburgGermany20246
    32Universitaetsklinikum HeidelbergHeidelbergGermany69120
    33Universitatsklinikum LeipzigLeipzigGermany04103
    34Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-GermanyTübingenGermany72076
    35Universitätsklinikum WürzburgWürzburgGermany97080
    36Sheba Medical Center Tel HashomerRamat GanIsrael52621
    37Tel-Aviv Sourasky Medical CenterTel-AvivIsrael64239
    38VU Medisch CentrumAmsterdamNetherlands1081 HV
    39University Medical Center GroningenGroningenNetherlands9713 GZ
    40King Faisal Specialist Hospital & Research CenterRiyadhSaudi Arabia11211
    41Clinica Univ. de NavarraPamplonaSpain31008
    42Hosp. Clinico Univ. de SalamancaSalamancaSpain37007

    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:
    NCT04133636
    Other Study ID Numbers:
    • CR108581
    • 2018-004124-10
    • 68284528MMY2003
    First Posted:
    Oct 21, 2019
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 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
    Keywords provided by Janssen Research & Development, LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021