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Studie for å evaluere effekten av Brexucabtagene Autoleucel (KTE-X19) hos deltakere med residiverende/refraktært mantelcellelymfom (Kohort 3) (ZUMA-2)

24. juli 2026 oppdatert av: Kite, A Gilead Company

En fase 2 multisenterstudie som evaluerer effekten av KTE-X19 hos personer med residiverende/refraktær mantelcellelymfom

Hovedmålet er å evaluere effekten av brexucabtagene autoleucel (KTE-X19) hos deltakere med residiverende/refraktær (r/r) mantelcellelymfom (MCL) i kohort 3 av denne studien.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Studie KTE-C19-102 (NCT02601313) registrerte deltakere med r/r MCL som har blitt behandlet med opptil 5 tidligere regimer, inkludert en Brutons tyrosinkinasehemmer (BTKi) i kohort 1 og kohort 2. Imidlertid for å oppfylle FDA Postmarketing Requirement Cohort 3 er lagt til studiet. Det vil inkludere deltakere med r/r MCL som har blitt behandlet med opptil 5 tidligere regimer, men som ikke har mottatt tidligere terapi med en BTKi.

Primæranalysen i kohort 1 og kohort 2 er allerede fullført. Data for kohort 3 vil bli analysert separat. Derfor er denne separate registreringen kun for kohort 3.

Etter slutten av KTE-C19-102 vil forsøkspersoner som fikk en infusjon av anti-CD19 CAR T-celler fullføre resten av 15-års oppfølgingsvurderingene i en egen langtidsoppfølgingsstudie, KT-US- 982-5968

Studietype

Intervensjonell

Registrering (Faktiske)

95

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Arizona
      • Gilbert, Arizona, Forente stater, 85234
        • Banner MD Anderson Cancer Center
    • California
      • Palo Alto, California, Forente stater, 94305
        • Stanford University
      • Santa Monica, California, Forente stater, 90404
        • University California Los Angeles (UCLA)
    • Colorado
      • Denver, Colorado, Forente stater, 80218
        • Sarah Cannon- Denver
    • Florida
      • Miami, Florida, Forente stater, 33136
        • University of Miami
      • Tampa, Florida, Forente stater, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, Forente stater, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, Forente stater, 60637
        • University of Chicago
      • Maywood, Illinois, Forente stater, 60153
        • Loyola University Medical Center
      • Park Ridge, Illinois, Forente stater, 60068
        • Advocate Aurora Health - Advocate Lutheran General Hospital
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, Forente stater, 48201
        • Karmanos Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, Forente stater, 07601
        • Hackensack University Medical Center
    • New York
      • Rochester, New York, Forente stater, 14642
        • University of Rochester
    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
        • Duke University
    • Ohio
      • Cleveland, Ohio, Forente stater, 44195
        • Cleveland Clinic - Taussig Cancer Institute
      • Columbus, Ohio, Forente stater, 43220
        • Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37232
        • Vanderbilt University
      • Nashville, Tennessee, Forente stater, 37203
        • Sarah Cannon - Tenessee
    • Texas
      • Dallas, Texas, Forente stater, 75246
        • Baylor Cancer Hospital
      • Houston, Texas, Forente stater, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, Forente stater, 98104
        • Swedish Cancer Institute
  • Frankrike
      • Montpellier, Frankrike, 34295
        • CHU de Montpellier
      • Paris, Frankrike, 75010
        • Hospital Saint Louis
      • Pessac, Frankrike, 44035
        • Hôpital Haut-Lévêque
      • Pierre-Bénite, Frankrike, 69495
        • Centre Hospitalier Lyon Sud
      • Rennes, Frankrike, 35033
        • CHU de RENNES
  • Nederland
      • Amsterdam, Nederland, 1100
        • Academisch Medisch Centrum
      • Groningen, Nederland, 9700 RB
        • University Medical Center Groningen
      • Rotterdam, Nederland, 3015 CE
        • Erasmus MC
  • Spania
      • Barcelona, Spania, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spania
        • Hospital Clinic Barcelona
      • Salamanca, Spania, 37007
        • Hospital Universitario de Salamanca
  • Storbritannia
      • Glasgow, Storbritannia, G51 4TF
        • Queen Elizabeth University Hospital
      • London, Storbritannia, SE5 9RS
        • Kings College Hospital
      • Manchester, Storbritannia, M13 9WL
        • Manchester Royal Infirmary
  • Tyskland
      • Mainz, Tyskland, 55101
        • Johannes Gutenberg University Hospital-University Mainz
      • München, Tyskland, 81377
        • Munich University of Technology-Medical Faculty- Ethics Committee
      • Würzburg, Tyskland, 97080
        • Universitaetsklinikum Wuerzburg

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Beskrivelse

Viktige inkluderingskriterier:

  • Opptil 5 tidligere regimer for MCL. Tidligere behandling må ha inkludert antracyklin- eller bendamustinholdig kjemoterapi og anti-CD20 monoklonalt antistoffbehandling. Enkeltpersoner må ikke ha mottatt tidligere behandling med en BTKi.
  • Minst 1 målbar lesjon
  • Blodplateantall ≥ 75 000/uL
  • Kreatininclearance (som estimert av Cockcroft Gault) ≥ til 60 cc/min
  • Kardial ejeksjonsfraksjon ≥ 50 %, ingen tegn på perikardiell effusjon bestemt ved et ekkokardiogram (ECHO) eller multigated acquisition (MUGA), og ingen klinisk signifikante elektrokardiogram (EKG) funn
  • Baseline oksygenmetning > 92 % på romluft

Nøkkelekskluderingskriterier:

  • Kjent historie med infeksjon med humant immunsviktvirus (HIV) eller hepatitt B (HBsAG-positiv) eller hepatitt C-virus (anti-HCV-positiv). Personer med en historie med hepatittinfeksjon må ha fjernet infeksjonen som bestemt ved standard serologisk og genetisk testing
  • Anamnese med anfallsforstyrrelse, cerebrovaskulær iskemi/blødning, demens, cerebellar sykdom, cerebralt ødem, posterior reversibelt encefalopatisyndrom eller enhver autoimmun sykdom med sentralnervesystemet (CNS) involvering
  • Tilstedeværelse av sopp, bakteriell, viral eller annen infeksjon som er ukontrollert eller som krever IV antimikrobielle midler for behandling

Merk: Andre protokolldefinerte kriterier for inkludering/ekskludering kan gjelde.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Brexucabtagene autoleucel (KTE-X19)

Participants with relapsed or refractory (r/r) mantle cell lymphoma (MCL) who have been treated with up to 5 prior regimens but have not received prior therapy with a Bruton's tyrosine kinase inhibitor (BTKi) will receive the following treatment during the study:

  • A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day for 3 days (Day -5 to Day -3).
  • A single infusion of brexucabtagene autoleucel at a target dose of 2×10^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg, with a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells for participants > 100 kg on Day 0.
Legemiddel: Fludarabine
Administered as intravenous infusion
Legemiddel: Cyclophosphamide
Administered as intravenous infusion
Biologisk: Brexucabtagene autoleucel
Administered as intravenous infusion
Andre navn:
  • Tecartus™
  • KTE-X19

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 3
Tidsramme: Up to 4 years
OR: complete metabolic response (CMR),complete radiological response (CRR), partial MR response (PMR),partial RR(PRR).CMR:score 1(no uptake above background)/2(uptake ≤mediastinum)/3(uptake >mediastinum but ≤liver) with/without a residual mass on positron emission tomography 5-point scale;no new lesions.CRR:target nodes/nodal masses regressed to ≤1.5cm in longest transverse diameter of lesion (LDi);no extralymphatic sites of disease;absent non-measured lesion(NMLs);organ enlargement regress to normal;no new sites;bone marrow normal by morphology. PMR:score 4(uptake moderately >liver)/5(uptake markedly >liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT). PRR: ≥50% decrease in sum of the product of the diameters(SPD) of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by >50% in length beyond normal.
Up to 4 years

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Prosentandel av deltakere med anti-CD19 CAR-antistoffer
Tidsramme: Baseline opp til måned 3
Baseline opp til måned 3
Toppserumnivåer av C-reaktivt protein (CRP) i blod
Tidsramme: Baseline frem til uke 4
Peak ble definert som det maksimale post-baseline-nivået av cytokinet.
Baseline frem til uke 4
Duration of Response (DOR) Per the Lugano Classification According to IRRC in Cohort 3
Tidsramme: Up to 4 years
DOR: time from the first OR to progressive disease (PD)/death. It was determined using Kaplan-Meier (KM) estimates. PD: score 4 (uptake moderately > liver)/ 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma at interim/EOT assessment; new FDG-avid foci consistent with lymphoma rather than another etiology; new/recurrent FDG-avid foci in bone marrow; an individual node/lesion must be abnormal with: LDi > 1.5 cm, increase by ≥ 50% from cross-product of LDi and perpendicular diameter (PPD) nadir, increase in LDi or shortest axis perpendicular to the LDi from nadir, the splenic length must increase by > 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, the increase must be ≥ 2 cm from baseline; new/recurrent splenomegaly; new or clear progression of pre-existing NMLs; new lesion; new/recurrent bone marrow involvement.
Up to 4 years
Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 3
Tidsramme: Up to 4 years
BOR consisted of complete response (CR), partial response (PR), stable disease (SD), PD, not done and not evaluable (NE). CR=CMR/CRR and PR=PMR/PRR were defined in Outcome Measure (OM) 1. SD/no metabolic response (NMR): a score 4 (uptake moderately greater than (>) liver) or 5 (uptake markedly >liver and/ or new lesions) with no significant change in FDG uptake compared to baseline (screening), at an interim time point or end of treatment; no new sites of disease should be observed. PD was defined in OM 2. Not done: no assessment at the time of analysis. Clopper-Pearson method was used for OM analysis. Percentages were rounded off.
Up to 4 years
Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 3
Tidsramme: Up to 4 years
OR was defined in OM #1. Percentages were rounded-off.
Up to 4 years
Progression Free Survival (PFS) Per the Lugano Classification According to IRRC in Cohort 3
Tidsramme: Up to 4 years
PFS was defined as the time from brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD was defined in OM #2. Kaplan-Meier (KM) estimates were used for analysis.
Up to 4 years
Overall Survival (OS)
Tidsramme: Up to 4 years
OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. KM estimates were used for analysis.
Up to 4 years
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Tidsramme: Up to 3 years
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participants. The event did not necessarily have a relationship with study treatment. AE included worsening of a pre-existing medical condition. Worsening indicated that the pre-existing medical condition had increased in severity, frequency, and/or duration or had an association with a worse outcome. A pre-existing condition that had not worsened during the study or involved an intervention such as elective cosmetic surgery or a medical procedure while on study, was not considered an AE. TEAE was defined as any AE with onset on or after the start of treatment.
Up to 3 years
Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
Tidsramme: Up to 3 years
Laboratory results were graded according to National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE) version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Up to 3 years
Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
Tidsramme: Up to 3 years
Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Up to 3 years
Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
Tidsramme: Up to 3 years
Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Up to 3 years
Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
Tidsramme: Up to 3 years
Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Up to 3 years
Maximum Number of CAR T Cells Measured Post-infusion
Tidsramme: Up to Month 36
Up to Month 36
Peak Serum Levels of C-X-C Motif Chemokine 10 (CXCL10), Granzyme B, Interferon-gamma (IFN-γ), Interleukin (IL)-1 Receptor Antagonist (RA), IL-2, IL-6, IL-7, IL-8, IL-10, IL-15 and Tumor Necrosis Factor (TNF)-α in Blood
Tidsramme: Baseline up to Week 4
Peak was defined as the maximum post-baseline level of the cytokine.
Baseline up to Week 4
Peak Serum Levels of Ferritin, Intercellular Adhesion Molecule (ICAM)-1, IL-2 Receptor Alpha (Rα), Perforin and Vascular Cell Adhesion Molecule (VCAM)-1 in Blood
Tidsramme: Baseline up to Week 4
Peak was defined as the maximum post-baseline level of the cytokine.
Baseline up to Week 4
Percentage of Participants With European Quality of Life-5 Dimensions (EQ-5D) Scale Score at Different Timepoints
Tidsramme: Day 0, Month 18 and Month 24
The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) was a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant was asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, were converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. Percentage of participants with each scale score for all 5 dimensions are reported. Percentages were rounded-off.
Day 0, Month 18 and Month 24
EQ-5D Visual Analogue Scale (VAS) Score at Different Timepoints
Tidsramme: Day 0, Month 18 and Month 24
EQ-5D was a standardized participant completed questionnaire that measures health-related quality of life and translated the score into an index value or utility score. EQ-5D-consisted of two components: a health state profile and an optional visual analogue scale (VAS). The EQ-5D-VAS recorded the participant's self-rated health on a vertical visual analogue scale, where the endpoints were labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicated better self-reported health status.
Day 0, Month 18 and Month 24
Percentage of Participants With Deterioration Scores From Screening in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30
Tidsramme: Screening Day -28 to Leukapheresis (Day -5), Day 0, Month 18 and Month 24
EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status/quality of life (QoL) scale, symptom scales (fatigue, pain, nausea/vomiting), and single items scales (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged, transformed to 0-100 scale. Higher scores for functional scales and for the global health status/QoL scale indicate a higher level of functioning and a better health-related QoL, whereas higher scores in symptom scales represent a higher level of symptoms. Deterioration of score was defined as worsened by at least 1 level from screening. Participants with answer "Yes" to the EORTC functional scale questionnaire were reported.
Screening Day -28 to Leukapheresis (Day -5), Day 0, Month 18 and Month 24

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Kite, A Gilead Company

Etterforskere

  • Studieleder: Kite Study Director, Kite, A Gilead Company

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

23. april 2021

Primær fullføring (Faktiske)

17. juni 2025

Studiet fullført (Faktiske)

17. juni 2025

Datoer for studieregistrering

Først innsendt

30. april 2021

Først innsendt som oppfylte QC-kriteriene

5. mai 2021

Først lagt ut (Faktiske)

10. mai 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

18. august 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

24. juli 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • KTE-C19-102 (Cohort 3)
  • 2015-005008-27 (EudraCT-nummer)
  • 2023-506641-35 (Annen identifikator: European Medicines Agency)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Qualified external researchers may request IPD for this study. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment

IPD-delingstidsramme

18 months after study completion and at least 6 months after the FDA and EMA approval

Tilgangskriterier for IPD-deling

A secured external environment with username, password, and RSA code.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere