- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT07570563
Clinical Study of the Safety and Efficacy of Allogeneic TCR-enhanced Vδ2 T Cell in Patients With Malignant Tumors.
A Clinical Study on the Safety and Efficacy of Allogeneic TCR-enhanced Vδ2 T Cell Injection in the Treatment of Patients With Malignant Tumors
The allogeneic TCR-enhanced Vδ2 T cell product is a novel genetically engineered cellular therapeutic. By engineering a specific BTN protein-binding moiety on its cell surface, this product harnesses the intrinsic tumoricidal potential of endogenous Vδ2 T cells and augments BTN protein recognition capability, thereby significantly boosting tumor cell killing potency. Notably, this engineered cell product exhibits no expression of co-stimulatory signaling domains and CD3ζ domains. This design circumvents T cell exhaustion triggered by overactivation and markedly enhances the in vivo persistence of therapeutic cells.
This is an open, prospective, open-label Phase I/II clinical trial designed to assess the safety and therapeutic efficacy of allogeneic TCR-enhanced Vδ2 T cell injection in patients with relapsed or refractory hematologic malignancies and advanced solid tumors.
Studienübersicht
Status
Bedingungen
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienkontakt
- Name: Weidong Han
- Telefonnummer: +86-010-55499341
- E-Mail: hanwdrsw@163.com
Studienorte
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Beijing Municipality
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Beijing, Beijing Municipality, China, 100853
- Rekrutierung
- Biotherapeutic Department of Chinsese PLA Gereral Hospital
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Kontakt:
- Yang Liu, M.D
- Telefonnummer: +86 010-66939460
- E-Mail: liuyang301blood@163.com
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Kontakt:
- Weidong Han, PH.D
- Telefonnummer: +86 +86-010-66937463
- E-Mail: hanwdrsw@163.com
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Beschreibung
Inclusion Criteria:
- Age 18-75 (inclusive).
- Expected survival time ≥ 3 months.
- Meets current clinical diagnostic criteria with a confirmed diagnosis of a malignant hematologic tumor or solid tumor, and has failed standard therapy (for solid tumors, at least one evaluable lesion according to RECIST v1.1 is required).
- Adequate bone marrow reserve and essentially normal liver and kidney function (laboratory tests must meet the following criteria prior to the first allogeneic TCR-enhanced Vδ2 T cell treatment):
- Hematology: White Blood Cell Count (WBC) ≥ 2.5×10⁹/L, Lymphocyte Count (LY) ≥ 0.8×10⁹/L, Hemoglobin (Hb) ≥ 80 g/L, Platelets (PLT) ≥ 75×10⁹/L.
- Liver: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; Total Bilirubin ≤ 3.0 × ULN.
- Kidney: Serum Creatinine ≤ 1.5 × ULN.
- Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50% as measured by echocardiogram.
- Pulmonary: Normal oxygen saturation without supplemental oxygen.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1.
- A negative pregnancy test is required for women of childbearing potential. Both male and female subjects must agree to use effective contraception during the treatment period and for 1 year thereafter.
- Able to understand the trial requirements and is willing to participate in the clinical study as required.
- Voluntarily signs the informed consent form for the clinical trial.
Exclusion Criteria:
- Known history of allergy, hypersensitivity, intolerance, or contraindication to allogeneic TCR-enhanced Vδ2 T cell or any components of the study drugs (including fludarabine, cyclophosphamide and albumin paclitaxel).
- Continuous use of immunosuppressants within 1 month prior to allogeneic TCR-enhanced Vδ2 T cell infusion.
- History of cerebrovascular accident or seizure within 6 months prior to signing the informed consent.
- Symptomatic brain metastases.
- Known psychiatric or substance abuse disorders that would compromise compliance with study requirements.
- Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) with detectable Hepatitis B virus (HBV) DNA levels outside the normal reference range; positive for Hepatitis C virus (HCV) antibody with detectable HCV RNA; positive for Human Immunodeficiency Virus (HIV) antibody; positive for syphilis.
- Severe cardiac disease, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA Class ≥ III), and severe arrhythmia.
- Active or uncontrolled infection requiring systemic therapy (except for mild urogenital and upper respiratory tract infections).
- Has not recovered from acute toxic effects of prior therapy (i.e., persisting hematological or organ toxicity ≥ Grade 2 related to prior therapy, excluding abnormalities associated with the study disease and its history).
- Diagnosed with immunodeficiency.
- Active infection requiring systemic treatment.
- Female subjects of childbearing potential planning pregnancy within 2 years after cell infusion; or male subjects whose partners are planning pregnancy within 2 years after cell infusion.
- Participation in another investigational drug clinical study within 1 month prior to screening.
- Last anti-tumor therapy administered less than 5 half-lives of the drug prior to planned allogeneic TCR-enhanced Vδ2 T cell infusion.
- Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Patients with Relapsed/refractory hematologic malignancies and advanced solid tumor
A conditional chemotherapy regimen of fludarabine and cyclophosphamide(for patients with solid tumors, albumin paclitaxel will be used additionally) will be administered, followed by investigational therapy, allogeneic TCR-enhanced Vδ2 T cell.
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Allogeneic TCR-enhanced Vδ2 T cells in a standard 3+3 dose-escalation design. Three predefined dose levels are investigated: Dose 1: 1×10^7 enTCR Vδ2T cells/kg, Dose 2: 3×10^7 enTCR Vδ2T cells/kg, and Dose 3: 6×10^7 enTCR Vδ2T cells/kg. For patients with hematological tumors, cyclophosphamide should be administered from day 5 to day 3 before cell infusion, with a recommended dose of 500 - 1000 mg/m² per day. For patients with solid tumors, cyclophosphamide should be administered from day 4 to day 3 before cell infusion, with a recommended dose of 500 - 700 mg/m² per day. For patients with hematological tumors, fludarabine should be administered from day 5 to day 3 before cell infusion, and the recommended dose is 30 - 50 mg/m² per day. For patients with solid tumors, fludarabine should be administered from day 4 to day 3 before cell infusion, with a recommended dose of 30 - 40 mg/m² per day.
Andere Namen:
This is only applicable to patients with solid tumors.
It should be administered on the fifth day before cell infusion.
The recommended dosage is 150-200 mg/m² per day.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Adverse Event
Zeitfenster: 12 months
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AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic TCR-enhanced Vδ2 T cells infusion.
Among them, cytokine release syndrome (CRS), immune cell-associated neurotoxicity syndrome (ICANS) , graft-versushost disease (GVHD) are excluded .
Other AEs were graded according to the regulatory agency's Medical Dictionary for Regulatory Activities (MedDRA) and common terminology criteria for adverse events (CTCAE) v5.0
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12 months
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DLTs
Zeitfenster: 28 days after cell infusion
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DLT was defined as allogeneic TCR-enhanced Vδ2 T cells-related events with onset within first 28 days following infusion
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28 days after cell infusion
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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PD(Pharmacodynamics):changes over time
Zeitfenster: 12 months
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To monitor changes over time in the cytokines mainly include interleukin-2 (IL-2 ), IL-4,IL-6, interferon-γ(IFN-γ), Tumor Necrosis Factor-alpha (TNF-α).
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12 months
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Objective Response Rate
Zeitfenster: 12 months after cell infusion
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The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) are the response to treatment assessed by investigators.
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12 months after cell infusion
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PK(Pharmacokinetics):Number and Copy Number of allogeneic TCR-enhanced Vδ2 T cell
Zeitfenster: 12 months
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Number and copy number of allogeneic TCR-enhanced Vδ2 T cells were assessed by number in peripheral blood.
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12 months
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Overall Survival(OS)
Zeitfenster: 12 months
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OS is defined as the time from allogeneic TCR-enhanced Vδ2 T cell infusion to the date of death.
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12 months
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Progression Free Survival (PFS)
Zeitfenster: 12 months
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PFS is defined as the time from the allogeneic TCR-enhanced Vδ2 T cell infusion date to the date of disease progression assessed by investigators.
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12 months
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Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Neubildungen nach Standort
- Neubildungen
- Hämatologische Erkrankungen
- Hämische und lymphatische Krankheiten
- Hämatologische Neubildungen
- Organische Chemikalien
- Kohlenwasserstoffe
- Phosphoramid -Senf
- Stickstoffsenfverbindungen
- Senfverbindungen
- Kohlenwasserstoffe, halogeniert
- Phosphoramide
- Organophosphorverbindungen
- Cyclophosphamid
- Fludarabine
Andere Studien-ID-Nummern
- CHN-PLAGH-BT-100
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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