NCT07164560RecruitingPhase 1
Clinical Study of Umbilical Cord Blood-Derived CAR-NK Cell Therapy Targeting TRBC1/2 for Relapsed/Refractory T-Cell Lymphoma
Second Affiliated Hospital, School of Medicine, Zhejiang University1 site in 1 country45 target enrollmentStarted: April 1, 2026Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Incidence of dose limiting toxicity (DLTs)
Study Overview
Brief Summary
This study aims to evaluate the safety and efficacy of Umbilical Cord Blood-Derived CAR-NK Cell Therapy Targeting TRBC1/2 (TRBC1/2 CAR-NK 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-NK cell therapy in patients with TRBC1/2-positive T-cell lymphoma.
The study will be conducted in two parts:
Phase I (Dose Escalation):
A dose-escalation study will be carried out following the conventional "3+3" design, with one dose level administered via intravenous infusion. Each cohort will enroll 3 to 6 patients. After the initial infusion, patients will be observed for at least 28 days for safety evaluation, followed by long-term follow-up of up to 2 years post-infusion.
Phase II (Dose Expansion):
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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-NK 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/
- •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.
- •People who test positive for COVID-19 or influenza A virus.
Arms & Interventions
CB TRBC1/2 CAR-NK
Experimental
Intervention: Anti-TRBC1 CAR-T cells (Biological)
Outcomes
Primary Outcomes
Incidence of dose limiting toxicity (DLTs)
Time Frame: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of peripheral blood-derived Anti-TRBC1/2 CAR-T Cell Therapy for refractory/relapsed peripheral T-cell lymphoma.
Secondary Outcomes
- Complete response rate (CR)(3 months)
Investigators
Study Sites (1)
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