Status:

RECRUITING

Exploratory Study of TRBC1/2-Targeted CAR-T Cell Therapy in Relapsed/Refractory Peripheral T-Cell Lymphoma

Lead Sponsor:

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborating Sponsors:

Peking University Cancer Hospital & Institute

Ruijin Hospital

Conditions:

Refractory/Recurrent Peripheral T-cell Lymphoma

Eligibility:

All Genders

18-75 years

Phase:

PHASE1

Brief Summary

This study aims to evaluate the safety and efficacy of TRBC1/2-directed chimeric antigen receptor T cells (TRBC1/2 CAR-T cells) in patients with refractory or relapsed peripheral T-cell lymphoma (PTCL...

Detailed Description

This is a multicenter, open-label, single-arm, phase I clinical trial designed to evaluate the safety and efficacy of TRBC1/2 CAR-T cell therapy in patients with TRBC1/2-positive T-cell lymphoma. The...

Eligibility Criteria

Inclusion

  • Inclusion Criteria
  • According to the 2016 WHO classification of lymphoid neoplasms, patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) must meet the following criteria to be eligible for enrollment:
  • Voluntarily agree to participate in this study and provide signed informed consent.
  • Age 18 to 75 years, male or female.
  • Diagnosis of relapsed/refractory PTCL, defined as failure of ≥1 prior line of therapy. Eligible histologic subtypes include (but are not limited to):
  • Angioimmunoblastic T-cell lymphoma (AITL) Anaplastic large cell lymphoma (ALCL) Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)
  • Estimated life expectancy ≥12 weeks.
  • TRBC1/2-positive tumor tissue (≥20% by immunohistochemistry) OR TCR gene rearrangement confirmed by PCR or NGS.
  • ECOG performance status of 0-2.
  • Adequate organ function as defined below:
  • ALT and AST ≤ 2.5 × upper limit of normal (ULN) Creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min Total bilirubin ≤ 1.5 × ULN Left ventricular ejection fraction (LVEF) ≥ 50% Baseline oxygen saturation \> 92% on room air
  • Hematology:
  • Phase Ia: ANC \> 1500/mm³, platelets \> 75 × 10⁹/L, hemoglobin \> 9 g/dL Phase Ib: ANC \> 1000/mm³, platelets \> 50 × 10⁹/L, hemoglobin \> 8 g/dL
  • ≥3 months since prior autologous hematopoietic stem cell transplantation.
  • Prior CAR-T therapy targeting a different antigen is permitted if lack of efficacy was confirmed after ≥3 months of evaluation, or if complete remission (CR) was achieved but relapse occurred.
  • Women of childbearing potential must have a negative pregnancy test prior to enrollment. All patients (male and female) must agree to use effective contraception during the study.
  • Presence of at least one measurable lesion.
  • All approved prior anti-tumor therapies (including systemic chemotherapy, total body irradiation, or immunotherapy) must have been completed ≥3 weeks before study drug administration; for non-chemotherapy targeted agents, a washout period of ≥2 weeks is required.
  • Exclusion Criteria
  • Patients meeting any of the following criteria will be excluded from this study:
  • History of allergy to any component of the cell product.
  • History of another malignancy that has not achieved remission.
  • Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
  • Receipt of gene therapy within the past 3 months.
  • Uncontrolled systemic active infection (with the exception of simple urinary tract infection or bacterial pharyngitis). Prophylactic use of antibiotics, antivirals, or antifungal agents is permitted.
  • Active hepatitis B infection (HBsAg positive; however, patients with HBV-DNA \<10³ copies/mL are not excluded), active hepatitis C virus infection (including carriers), syphilis, or other acquired or congenital immunodeficiency diseases, including but not limited to HIV infection.
  • New York Heart Association (NYHA) Class III or IV heart failure.
  • Unresolved toxicity from prior anti-tumor therapy (defined as CTCAE v5.0 Grade \>1, with the exception of fatigue, anorexia, and alopecia).
  • Evidence of central nervous system (CNS) involvement at screening, or clinically significant CNS disease such as a history of seizures or other CNS disorders.
  • Prior exposure to any agent specifically targeting TRBC1/2.
  • Lactating women who are unwilling to discontinue breastfeeding.
  • Any other condition that, in the opinion of the investigator, may increase patient risk or interfere with the study results.
  • Autoimmune disease requiring immunosuppressive therapy.
  • Use of immunosuppressive agents or therapeutic doses of corticosteroids (defined as prednisone \>20 mg/day or equivalent) within 7 days prior to leukapheresis, or use of hematopoietic growth factors such as G-CSF. Physiological replacement therapy, topical, or inhaled corticosteroids are permitted.
  • Receipt of chemotherapy, targeted therapy, immunotherapy, or radiotherapy within 3 days prior to leukapheresis.
  • Participation in another clinical trial within 4 weeks or within 5 half-lives of the investigational product (whichever is shorter) prior to leukapheresis.

Exclusion

    Key Trial Info

    Start Date :

    September 1 2025

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    September 1 2028

    Estimated Enrollment :

    45 Patients enrolled

    Trial Details

    Trial ID

    NCT07164560

    Start Date

    September 1 2025

    End Date

    September 1 2028

    Last Update

    September 10 2025

    Active Locations (1)

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    2nd Affiliated Hospital,School of Medicine,Zhejiang University

    Hangzhou, Zhejiang, China