- ICH GCP
- Registre américain des essais cliniques
- Essai clinique 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.
Aperçu de l'étude
Statut
Les conditions
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Weidong Han
- Numéro de téléphone: +86-010-55499341
- E-mail: hanwdrsw@163.com
Lieux d'étude
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Beijing Municipality
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Beijing, Beijing Municipality, Chine, 100853
- Recrutement
- Biotherapeutic Department of Chinsese PLA Gereral Hospital
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Contact:
- Yang Liu, M.D
- Numéro de téléphone: +86 010-66939460
- E-mail: liuyang301blood@163.com
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Contact:
- Weidong Han, PH.D
- Numéro de téléphone: +86 +86-010-66937463
- E-mail: hanwdrsw@163.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
Autres noms:
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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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Adverse Event
Délai: 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
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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PD(Pharmacodynamics):changes over time
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs par site
- Tumeurs
- Maladies hématologiques
- Maladies hémiques et lymphatiques
- Tumeurs hématologiques
- Produits chimiques organiques
- Hydrocarbures
- Moutards phosphoramides
- Composés de moutarde d'azote
- Composés moutarde
- Hydrocarbures, halogénés
- Phosphoramides
- Composés organophosphores
- Cyclophosphamide
- fludarabine
Autres numéros d'identification d'étude
- CHN-PLAGH-BT-100
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
Informations sur les médicaments et les dispositifs, documents d'étude
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