Anti-CD5 CAR NK cells: Each patient will initially receive a single infusion of CAR-NK cells on Day 0. If a suboptimal response is observed after the first infusion (assessed by Day 28) and the safety profile remains acceptable, a second infusion may be administered as a remedial dose after Day 28. CAR-NK cells need to be controlled within 70 minutes from thawing to infusion completion.
Study summary
This is a clincal trial initiated by investigator to evaluate the safety and efficacy of anti-CD5 CAR-NK in the treatment of patients with relapsed/refractory T-Cell hematologic malignancies.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria:
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1.Gender and Age: No gender restriction; age 18-75 years (inclusive). 2.Diagnosis: Confirmed diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoma, including:
1. T-ALL Patients: Bone marrow morphology during screening shows ≥5% blasts/immature lymphocytes and/or flow cytometry confirms minimal residual disease (MRD)+, and meets any of the following:
1. Refractory to ≥2 cycles of standard induction chemotherapy (failure to achieve CR).
2. Relapsed within 12 months after achieving CR with first-line induction therapy.
3. Failure to achieve CR or relapse after ≥2 lines of chemotherapy.
4. Relapse after hematopoietic stem cell transplantation (HSCT).
2. T-cell Lymphoma Patients: Confirmed diagnosis of T-lymphoblastic lymphoma (T-LBL) or T-cell non-Hodgkin lymphoma (including but not limited to: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), extranodal NK/T-cell lymphoma (ENKL), T-cell prolymphocytic leukemia (T-PLL), adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides/Sézary syndrome (MF/SS) stage IIB or higher), and meets both:
1. At least one bidimensionally measurable lesion per Lugano 2014 criteria: nodal lesions \>1.5 cm in long axis; extranodal lesions \>1.0 cm in long axis.
2. Refractory to ≥2 lines of chemotherapy, primary resistance, or relapse post-HSCT.
3.CD5 Positivity: Confirmed by flow cytometry (≥80% tumor cells express CD5 with mean fluorescence intensity \[MFI\] equivalent to normal T cells; Dim defined as MFI ≥1 log lower than normal T cells; partial positivity defined as 20-80% tumor cells expressing CD5) or immunohistochemistry (\>30% tumor cells express CD5).
4.ECOG Performance Status: 0-2 . 5.Life Expectancy: ≥12 weeks. 6.Organ Function:
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1. Cardiac: Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; no significant ECG abnormalities.
2. Renal: Serum creatinine ≤2.0×ULN.
3. Hepatic: ALT/AST ≤3.0×ULN (≤5.0×ULN if liver involvement); total bilirubin ≤2.0×ULN.
4. Pulmonary: Oxygen saturation ≥92% (room air). 7.No Contraindications: To leukapheresis, venipuncture, or cell collection. 8.No Severe Psychiatric Disorders. 9.Contraception: Agreement to use effective contraception from informed consent until 1 year post-CAR-NK infusion (for patients of childbearing potential).
10.Informed Consent: Signed by the patient or legal guardian, confirming understanding of the trial's purpose and procedures.
Exclusion Criteria:
1. Prior CAR-NK therapy or genetically modified cell therapy.
2. Active CNS involvement at screening (prior CNS involvement with resolved status post-treatment is allowed).
3. Recent Anticancer Therapy:
1. Chemotherapy, targeted therapy, or investigational drugs within 2 weeks or 5 half-lives prior to screening.
2. Radiotherapy within 2 weeks prior to screening.
4. Active/Uncontrolled Infection: Within 1 week prior to screening.
5. Cerebrovascular Event or Seizure: Within 6 months prior to screening.
6. Viral Infections:
1. HBV DNA \> ULN (if HBsAg+ or HBcAb+).
2. HCV RNA \> ULN (if HCV Ab+).
3. HIV+, syphilis+, or active tuberculosis.
7. Cardiac Disease:
1. NYHA Class III/IV congestive heart failure.
2. Myocardial infarction or CABG ≤6 months prior.
3. Clinically significant ventricular arrhythmia or unexplained syncope (excluding vasovagal/dehydration-related).
4. Severe cardiomyopathy.
8. Active/Uncontrolled Autoimmune Disease.
9. Prior Malignancy: Within 5 years, except for cured cervical carcinoma in situ, basal/squamous skin cancer, localized prostate cancer, or ductal carcinoma in situ.
10. Live Vaccination: Within 4 weeks prior to screening.
11. Pregnancy/Lactation: Pregnant, breastfeeding, or planning pregnancy within 1 year post-CAR-NK infusion.
12. Other: Investigator-determined ineligibility.
Primary outcome measure(s)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] — 28 dyas The incidence of adverse events after CAR-NK cell infusion was assessed by CTCAE, version 5.0.
Objective response rate (ORR) — 1month, 2 months, 3 months Objective Response Rate (ORR) within 3 Months:
1. For patients with T-cell lymphoma, ORR includes complete response (CR) and partial response (PR);
2. For patients with T-cell acute lymphoblastic leukemia (T-ALL), ORR includes CR, CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS).
Overall survival (OS) after CAR-NK infusion — 2 years OS is defined as the time from CAR-NK cell infusion to death from any cause, reflecting the long-term survival benefit of the therapy.
Duration of response (DOR) after CAR-NK infusion — 2 years DOR measures the time from the first achievement of objective response to disease progression or death, evaluating the durability of treatment efficacy in responding patients.
Progression-Free-Survival (PFS) after CAR-NK infusion — 2 years PFS is the time from CAR-NK cell infusion to disease progression or death from any cause, capturing both tumor control and survival outcomes
Trial sites (1)
Facility
City
Region
Status
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan
Hubei
Recruiting
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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