Umbilical cord blood CAR‑NK cells targeting TRBC1/2 for relapsed or refractory peripheral T‑cell lymphoma

Clinical Study of Umbilical Cord Blood-Derived CAR-NK Cell Therapy Targeting TRBC1/2 for Relapsed/Refractory T-Cell Lymphoma

This will test whether umbilical cord blood‑derived CAR‑NK cells that target TRBC1/2 are safe and can help people with relapsed or refractory peripheral T‑cell lymphoma.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07164560 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open‑label, single‑arm Phase I study using umbilical cord blood‑derived CAR‑NK cells directed at TRBC1/2 in patients with relapsed or refractory peripheral T‑cell lymphoma. Phase I uses a conventional 3+3 dose‑escalation design with one intravenous dose level and 28‑day safety observation, followed by long‑term follow‑up up to 2 years. If safety, in vivo expansion/persistence, and early efficacy are acceptable, a dose‑expansion cohort of about 30 patients will be enrolled to further characterize safety and preliminary efficacy. The trial requires documented TRBC1/2 positivity by IHC or TCR gene rearrangement and monitors organ function and performance status throughout.

Who should consider this trial

Good fit: Adults aged 18–75 with relapsed or refractory peripheral T‑cell lymphoma who are TRBC1/2‑positive (≥20% by IHC or confirmed TCR rearrangement), have ECOG 0–2, adequate organ function, and an expected survival of at least 12 weeks are ideal candidates.

Not a fit: Patients whose tumors do not express TRBC1/2, who have poor organ function, ECOG >2, or life expectancy under 12 weeks are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, this targeted CAR‑NK approach could provide an off‑the‑shelf cellular therapy that selectively eliminates TRBC1/2‑positive malignant T cells and potentially produces durable remissions with a different safety profile than CAR‑T.

How similar studies have performed: CAR‑T therapies targeting T‑cell antigens have shown activity but are limited by fratricide and toxicity, and CAR‑NK approaches are relatively novel with mainly preclinical or very early clinical evidence supporting their use.

Eligibility criteria

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:

1. Voluntarily agree to participate in this study and provide signed informed consent.
2. Age 18 to 75 years, male or female.
3. 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)
4. Estimated life expectancy ≥12 weeks.
5. TRBC1/2-positive tumor tissue (≥20% by immunohistochemistry) OR TCR gene rearrangement confirmed by PCR or NGS.
6. ECOG performance status of 0-2.
7. 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
8. ≥3 months since prior autologous hematopoietic stem cell transplantation.
9. 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.
10. 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.
11. Presence of at least one measurable lesion.
12. 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:

1. History of allergy to any component of the cell product.
2. History of another malignancy that has not achieved remission.
3. Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
4. Receipt of gene therapy within the past 3 months.
5. 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.
6. 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.
7. New York Heart Association (NYHA) Class III or IV heart failure.
8. Unresolved toxicity from prior anti-tumor therapy (defined as CTCAE v5.0 Grade \>1, with the exception of fatigue, anorexia, and alopecia).
9. Evidence of central nervous system (CNS) involvement at screening, or clinically significant CNS disease such as a history of seizures or other CNS disorders.
10. Prior exposure to any agent specifically targeting TRBC1/2.
11. Lactating women who are unwilling to discontinue breastfeeding.
12. Any other condition that, in the opinion of the investigator, may increase patient risk or interfere with the study results.
13. People who test positive for COVID-19 or influenza A virus.

Where this trial is running

Hangzhou, Zhejiang

• 2nd Affiliated Hospital,School of Medicine,Zhejiang University — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Wenbin Qian, professor

Conditions: Refractory/Recurrent Peripheral T-cell Lymphoma, Refractory/recurrent, Peripheral T-cell lymphoma, TRBC1/2 CAR-NK