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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 agosto 2026 aggiornato da: 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).

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Stimato)

70

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

  • Nome: Wenbin Qian,Professor
  • Numero di telefono: +86 13605801032
  • Email: qianwb@zju.edu.cn

Backup dei contatti dello studio

Luoghi di studio

  • Cina
    • Zhejiang
      • Hangzhou, Zhejiang, Cina, 310009
        • Reclutamento
        • The Second Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, Zhejiang 310009
        • Contatto:
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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).

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 7×19-THEMIS CAR-T
A single dose intravenous injection of 7X19-Themis at day 0
Biologico: 7×19-THEMIS CAR-T cells
IL7 and CCL19 Armed anti-CD19 CAR-T with coexpressing Themis

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Determination of the Recommended Phase II Dose (RP2D)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Single-Cell Functional Characterization of CAR-T Products
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Second Affiliated Hospital, Zhejiang University, School of Medicine

Investigatori

  • Cattedra di studio: Wenbin Qian,Professor, Second Affiliated Hospital, Zhejiang University, School of Medicine

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 settembre 2026

Completamento primario (Stimato)

1 settembre 2029

Completamento dello studio (Stimato)

1 settembre 2031

Date di iscrizione allo studio

Primo inviato

12 agosto 2026

Primo inviato che soddisfa i criteri di controllo qualità

23 agosto 2026

Primo Inserito (Effettivo)

26 agosto 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

26 agosto 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

23 agosto 2026

Ultimo verificato

1 agosto 2026

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2026-0675

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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