Hematologic Malignancy, Solid Tumor
Conditions
Brief summary
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.
Interventions
BIOLOGICALAllogeneic TCR-enhanced Vδ2 T cell Injection
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.
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.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 12 months | 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 |
| DLTs | 28 days after cell infusion | DLT was defined as allogeneic TCR-enhanced Vδ2 T cells-related events with onset within first 28 days following infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK(Pharmacokinetics):Number and Copy Number of allogeneic TCR-enhanced Vδ2 T cell | 12 months | Number and copy number of allogeneic TCR-enhanced Vδ2 T cells were assessed by number in peripheral blood. |
| PD(Pharmacodynamics):changes over time | 12 months | 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). |
| Objective Response Rate | 12 months after cell infusion | The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) are the response to treatment assessed by investigators. |
| Overall Survival(OS) | 12 months | OS is defined as the time from allogeneic TCR-enhanced Vδ2 T cell infusion to the date of death. |
| Progression Free Survival (PFS) | 12 months | 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. |
Countries
China
Contacts
CONTACTWeidong Han
Outcome results
None listed