CD70-targeted CAR-NK cell therapy for T‑cell lymphoma and acute myeloid leukemia

Cord Blood-derived CD70-targeting CAR-NK Cell Therapy for Refractory/Relapsed T Cell Lymphoma and Acute Myeloid Leukemia

This study will try CD70-targeted CAR-NK cell therapy in adults with relapsed or refractory T‑cell lymphoma or acute myeloid leukemia to see if it is safe and can help control the disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: Brentuximab, chemotherapy, immunotherapy, CAR-T, Chimeric antigen receptor
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06696846 on ClinicalTrials.gov

What this trial studies

This Phase 1, single-center trial gives engineered natural killer (CAR-NK) cells that target CD70 to adults with relapsed or refractory T‑cell lymphoma or acute myeloid leukemia to characterize safety, pharmacokinetics, and early signs of anti‑tumor activity. CD70 is commonly overexpressed on these tumor cells but minimally present on normal tissues, making it a selective target for cell therapy. CAR-NK cells may reduce risks seen with CAR-T approaches, such as fratricide and severe cytokine release, and preclinical models showed tumor control and extended survival without major toxicities. Participants must meet eligibility criteria including age 18–75 and CD70-positive relapsed/refractory disease and will be treated at a single site in Hangzhou, Zhejiang.

Who should consider this trial

Good fit: Adults aged 18–75 with CD70-positive relapsed or refractory T‑cell lymphoma (after at least two prior lines of therapy for most subtypes) or relapsed/refractory acute myeloid leukemia are the intended candidates.

Not a fit: Patients whose tumors lack CD70 expression or who have poor organ function, uncontrolled infections, or other medical conditions that prevent receiving cell therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could offer a new targeted cell therapy that controls CD70-positive TCL and AML with potentially fewer severe immune-related side effects than current options.

How similar studies have performed: Preclinical studies of CD70-directed CAR‑NK cells have shown tumor suppression and survival benefit in mouse models, but clinical data in humans are very limited and this is an early-phase clinical translation.

Eligibility criteria

Inclusion Criteria:

According to the WHO disease classification, patients with relapsed/refractory T - lymphoma and acute myeloid leukemia:

1. Voluntarily participate in this study and sign the informed consent form;
2. Aged between 18-75 years old, both male and female are eligible;
3. Relapsed/refractory T cell lymphoma is defined as: relapsed/refractory after having received at least two or more lines of previous treatment (patients with anaplastic large -cell lymphoma must have been exposed and resistant to Brentuximab vedotin). The celluar subtypes of T-cell lymphoma include: angioimmunoblastic T-cell lymphoma; peripheral T - cell lymphoma not otherwise specified; ALK-negative anaplastic large - cell lymphoma; Relapsed/refractory AML is defined as: leukemia cells reappear in the peripheral blood after complete remission or the blasts in the bone marrow ≥ 5% or the extramedullary leukemia infiltration outside. Or newly diagnosed cases did not achieve a CR after two courses of standard regimens; those who relapse within 12 months after CR after consolidation and intensification treatment; those who relapse after 12 months and have not responded to conventional chemotherapy; those who relapse two or more times; those with persistent extramedullary leukemia;
4. The expected survival period ≥ 12 weeks;
5. CD70 expression is positive in tumor tissue puncture sections/tumor cells detected by flow cytometry, and the number of CD70 - positive cells detected by immunohistochemistry ≥ 20% (++ or more);
6. ECOG score is 0 - 2;
7. Adequate organ function reserve:

   * Alanine aminotransferase and aspartate aminotransferase ≤ 2.5× UNL;
   * Creatinine clearance rate (Cockcroft - Gault method) ≥ 60 mL/min;
   * Serum total bilirubin and alkaline phosphatase ≤ 1.5× UNL;
   * Glomerular filtration rate \> 50 ml/min;
   * Cardiac ejection fraction ≥ 45%;
   * Under indoor natural air environment, the basic oxygen saturation \> 92%;
   * Routine blood test: absolute neutrophil count \> 1000/mm3, platelet count ≥ 45×109, hemoglobin ≥ 8.0g/dl (the standard for AML patients is ≥ 7.0g/dl; blood transfusion is allowed);
8. Previous autologous hematopoietic stem cell transplantation is allowed once;
9. Patients who have previously received CAR - T cell therapy and were evaluated as ineffective after 3 months or relapsed after CR are allowed;
10. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial period;
11. No active lung infection, and indoor air blood oxygen saturation ≥ 92%;
12. Before the study drug is used, approved anti - tumor treatment methods, such as systemic chemotherapy, whole - body radiotherapy, and immunotherapy, have been completed for at least 3 weeks; the wash - out period for targeted drug regimens without chemotherapy is 2 weeks;
13. Two negative tests for COVID - 19 or influenza A.

Exclusion Criteria:

Subjects meeting any of the following criteria will not be eligible for this study:

1. Those with a history of allergy to any component in the cellular product;
2. Those with a history of other tumors;
3. Those who had grade II - IV (Glucksberg criteria) acute GvHD or extensive chronic GvHD after previous allogeneic hematopoietic stem cell transplantation; or those who are currently receiving anti - GvHD treatment;
4. Those who have received gene therapy within the past 3 months;
5. Those with active infections requiring treatment (except for simple urinary tract infections and bacterial pharyngitis). However, prophylactic antibiotic, antiviral, and antifungal treatments are permitted;
6. Subjects with hepatitis B (HBsAg - positive, but HBV - DNA \< 103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis, and other acquired or congenital immunodeficiency diseases, including but not limited to those infected with the AIDS virus;
7. Subjects with grade III or IV cardiac insufficiency according to the New York Heart Association cardiac function classification standard of the United States;
8. Those whose toxic reactions from previous anti - tumor treatment have not recovered (CTCAE 5.0 toxic reactions have not recovered to ≤ grade 1, except for fatigue, anorexia, and alopecia);
9. Subjects with a history of epilepsy or other central nervous system diseases;
10. Lactating women who are unwilling to stop breastfeeding;
11. Any other circumstances that, in the opinion of the investigator, may increase the risk to the subject or interfere with the test results;
12. Those with positive nucleic acid tests for COVID - 19 or influenza A.

Where this trial is running

Hangzhou, Zhejiang

• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Wenbin Qian

Conditions Relapsed/Refractory T-cell Lymphoma; Relapsed/Refractory Acute Myeloid Leukemia; CD70; CAR-NK; T cell lymphoma; acute myeloid leukemia