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A Phase Ib/II Exploratory Clinical Trial of Memory-Enhanced 7×19-THEMIS CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma

23. august 2026 opdateret af: Second Affiliated Hospital, Zhejiang University, School of Medicine

A Phase Ib/II Exploratory Clinical Trial of Memory-Enhanced 7×19-THEMIS CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: A Single-Arm Design Using a Historical Control (7×19 CAR-T)

This study is aimed to explored the safety and efficacy of 7×19-THEMIS CAR-T cell therapy for large B-cell lymphoma and to conduct an exploratory comparison of the 3-month objective response rate (ORR) and complete remission rate (CR rate) between the experimental cohort and the historical control cohort (NCT04833504).

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

70

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

  • Navn: Wenbin Qian,Professor
  • Telefonnummer: +86 13605801032
  • E-mail: qianwb@zju.edu.cn

Undersøgelse Kontakt Backup

Studiesteder

  • Kina
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310009
        • Rekruttering
        • The Second Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, Zhejiang 310009
        • Kontakt:
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion Criteria:

  1. Voluntarily participate in this study and sign the informed consent form.
  2. Age range: 18 - 75 years old. Gender is not restricted.
  3. Histologically confirmed large B-cell lymphoma, including: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), and mantle cell lymphoma (MCL).
  4. CD19-positive (as determined by immunohistochemistry or flow cytometry; based on the most recent tumor biopsy results).
  5. Definition of relapsed/refractory: Failure to achieve complete remission (CR) after at least two lines of therapy (which must include a CD20 monoclonal antibody and an anthracycline); or disease progression during any course of treatment; or relapse/progression within 12 months after autologous hematopoietic stem cell transplantation.
  6. At least one measurable lesion: any lymph node lesion with a longest dimension >1.5 cm, or any extranodal lesion with a longest dimension >1.0 cm, and the lesion shows uptake on PET-CT (SUV greater than the hepatic pool).
  7. Absolute neutrophil count in peripheral blood ≥ 1,000/μL; platelet count ≥ 45,000/μL.
  8. Cardiac, hepatic, and renal function: creatinine < 1.5 mg/dL; ALT/AST ≤ 2.5 times the upper limit of normal; total bilirubin < 1.5 mg/dL; ejection fraction ≥ 50%.
  9. Possess sufficient cognitive capacity to voluntarily sign the informed consent form.
  10. Participants of reproductive potential must be willing to use effective contraception (from the time of signing the informed consent form until 12 months after CAR-T infusion).
  11. The investigator estimates a life expectancy of at least 4 months.
  12. Willing to comply with the schedule of visits, dosing regimen, laboratory tests, and other trial procedures.

Exclusion Criteria:

  1. History of other malignant tumors (excluding cured basal cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc.).
  2. Autologous hematopoietic stem cell transplantation within the past 6 weeks.
  3. Any targeted CAR-T therapy within 3 months prior to this CAR-T treatment.
  4. Patients who have previously received PD-1 monoclonal antibodies must have a washout period of ≥3 months before enrollment.
  5. Received cytotoxic drugs, glucocorticoids (except for prednisone-equivalent doses of ≤10 mg/day), or other targeted therapies within 2 weeks prior to cell collection.
  6. Active autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease, etc.).
  7. Uncontrolled active bacterial, fungal, or viral infections.
  8. HIV infection, syphilis; active hepatitis B or C: Hepatitis B: HBsAg-positive and HBV-DNA ≥ 1,000 IU/mL; Hepatitis C: HCV RNA-positive and abnormal liver function.
  9. Known central nervous system lymphoma (confirmed by brain MRI or CT and cerebrospinal fluid examination).

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 7×19-THEMIS CAR-T
A single dose intravenous injection of 7X19-Themis at day 0
Biologisk: 7×19-THEMIS CAR-T cells
IL7 and CCL19 Armed anti-CD19 CAR-T with coexpressing Themis

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Determination of the Recommended Phase II Dose (RP2D)
Tidsramme: Up to 3 months
Based on the incidence of DLTs, CAR-T cell kinetics, preliminary efficacy, and safety data from the Phase Ib dose-escalation phase, the Safety Review Committee (SRC) determined the RP2D following a comprehensive evaluation.
Up to 3 months
Objective Response Rate (ORR)
Tidsramme: Up to 3 months
At 3 months (±7 days) after infusion, the proportion of patients achieving complete remission (CR) or partial remission (PR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.
Up to 3 months
Complete Remission Rate (CR Rate)
Tidsramme: Up to 3 months
At 3 months (±7 days) after infusion, the proportion of patients who achieved complete remission (CR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.
Up to 3 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria
Tidsramme: up to 28 days
The incidence and severity of CRS and ICANS will be assessed according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria. The incidence of each grade (Grades 1-4) will be summarized, with particular attention to the incidence of Grade ≥3 CRS and Grade ≥3 ICANS.
up to 28 days
Incidence and duration of Grade ≥3 hematologic toxicities assessed according to CTCAE version 5.0
Tidsramme: up to 28 days
The incidence and duration of Grade ≥3 neutropenia, anemia, and thrombocytopenia will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
up to 28 days
Incidence of clinically significant infections requiring anti-infective treatment or hospitalization
Tidsramme: up to 28 days
The incidence of bacterial, fungal, and viral infections requiring anti-infective treatment or hospitalization will be recorded and summarized.
up to 28 days
Progression-Free Survival (PFS)
Tidsramme: up to 2-5 years
Progression-free survival is defined as the time from CAR-T cell infusion to the first documented disease progression (PD) or death from any cause, whichever occurs first. Median PFS and PFS rates at 12 and 24 months will be estimated using the Kaplan-Meier method.
up to 2-5 years
Overall Survival (OS)
Tidsramme: up to 2-5 years
Overall survival is defined as the time from CAR-T cell infusion to death from any cause. Median OS and OS rates at 12 and 24 months will be estimated using the Kaplan-Meier method.
up to 2-5 years
Duration of Response (DOR)
Tidsramme: up to 2-5 years
Among participants who achieve complete response (CR) or partial response (PR), duration of response is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first. Median DOR will be estimated using the Kaplan-Meier method.
up to 2-5 years
In Vivo Kinetics of CAR-T Cells
Tidsramme: up to 2-5 years
Measurement of CAR-T Cell Counts in Peripheral Blood and Comparison of Kinetic Parameters
up to 2-5 years
Serum Cytokine Dynamics
Tidsramme: day-5,day4,day7,day11,day14,day18,day21,day28,month 3
Measure the concentrations of cytokines such as IL-6, IFN-γ, IL-7, and CCL19 in serum at various time points following infusion.
day-5,day4,day7,day11,day14,day18,day21,day28,month 3
B-Cell Recovery
Tidsramme: month1, month3, month6, month9, months12, month24, year3 and year5
Determine the absolute count of CD19+CD20+ cells in peripheral blood to assess the dynamics of B-cell recovery following infusion.
month1, month3, month6, month9, months12, month24, year3 and year5

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Single-Cell Functional Characterization of CAR-T Products
Tidsramme: day-5, day4, day7, day11, day14, day18, day21, day28, month2
Detection of various cytokines secreted by CAR-T infusion products at the single-cell level upon stimulation with the CD19 antigen.
day-5, day4, day7, day11, day14, day18, day21, day28, month2
Spearman correlation between memory T-cell subset proportions in the CAR-T infusion product and 3-month complete response
Tidsramme: day-5, day4, day7, day11, day14, day18, day21, day28, month3
The proportions of stem cell memory T cells (TSCM), central memory T cells (TCM), effector memory T cells (TEM), and terminal effector T cells (TTE) in the CAR-T infusion product will be measured by multicolor flow cytometry. T-cell subsets will be defined as TSCM (CD45RA+CCR7+CD95+), TCM (CD45RA-CCR7+), TEM (CD45RA-CCR7-), and TTE (CD45RA+CCR7-). The proportion of each subset will be expressed as the percentage of CAR-T cells. The correlation between memory T-cell subset proportions and complete response at 3 months will be assessed using Spearman rank correlation and exploratory group comparisons using the Mann-Whitney U test.
day-5, day4, day7, day11, day14, day18, day21, day28, month3
Trends in Anti-CAR Antibodies (ADA)
Tidsramme: day-5, day4, day7, day11, day14, day18, day21, day28, month3,month6,month12, year2 and year5
Determination of the Prevalence and Titer of Anti-FMC63 Antibodies (ADA) in Serum
day-5, day4, day7, day11, day14, day18, day21, day28, month3,month6,month12, year2 and year5
Area under the receiver operating characteristic curve (AUC) of peak serum cytokine and chemokine levels within 28 days after CAR-T infusion for discrimination of objective response
Tidsramme: month6, month12, year2, year5
Peak serum concentrations of IL-7, CCL19, MIP-1α, MIP-1β, and SDF-1α during the first 28 days after CAR-T cell infusion will be measured using the protocol-specified serum cytokine/chemokine assay. Receiver operating characteristic (ROC) curve analysis will be performed to evaluate the ability of each biomarker to discriminate objective response, defined as complete response or partial response according to protocol-defined disease response criteria. The AUC and the optimal biomarker cutoff value will be determined for each biomarker.
month6, month12, year2, year5

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Second Affiliated Hospital, Zhejiang University, School of Medicine

Efterforskere

  • Studiestol: Wenbin Qian,Professor, Second Affiliated Hospital, Zhejiang University, School of Medicine

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. september 2026

Primær færdiggørelse (Anslået)

1. september 2029

Studieafslutning (Anslået)

1. september 2031

Datoer for studieregistrering

Først indsendt

12. august 2026

Først indsendt, der opfyldte QC-kriterier

23. august 2026

Først opslået (Faktiske)

26. august 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

26. august 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

23. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2026-0675

Plan for individuelle deltagerdata (IPD)

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