Clinical Trial of CD5-targeted CAR-NK Therapy for Relapse/Refractory T-Cell Hematologic Malignancies

Korábbi kezelés

• Prior CAR-NK therapy or genetically modified cell therapy.
• Active CNS involvement at screening (prior CNS involvement with resolved status post-treatment is allowed).
• Recent Anticancer Therapy:
  • Chemotherapy, targeted therapy, or investigational drugs within 2 weeks or 5 half-lives prior to screening.
  • Radiotherapy within 2 weeks prior to screening.
• Active/Uncontrolled Infection: Within 1 week prior to screening.
• Cerebrovascular Event or Seizure: Within 6 months prior to screening.
• Cardiac Disease:
  • NYHA Class III/IV congestive heart failure.
  • Myocardial infarction or CABG ≤6 months prior.
  • Clinically significant ventricular arrhythmia or unexplained syncope (excluding vasovagal/dehydration-related).
  • Severe cardiomyopathy.
• Live Vaccination: Within 4 weeks prior to screening.

Más betegség

• Active/Uncontrolled Autoimmune Disease.
• Prior Malignancy: Within 5 years, except for cured cervical carcinoma in situ, basal/squamous skin cancer, localized prostate cancer, or ductal carcinoma in situ.

Laborértékek

• Viral Infections:
  • HBV DNA > ULN (if HBsAg+ or HBcAb+).
  • HCV RNA > ULN (if HCV Ab+).
  • HIV+, syphilis+, or active tuberculosis.

Egyéb

• Pregnancy/Lactation: Pregnant, breastfeeding, or planning pregnancy within 1 year post-CAR-NK infusion.
• Other: Investigator-determined ineligibility.

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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:
• 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:
  • Refractory to ≥2 cycles of standard induction chemotherapy (failure to achieve CR).
  • Relapsed within 12 months after achieving CR with first-line induction therapy.
  • Failure to achieve CR or relapse after ≥2 lines of chemotherapy.
  • Relapse after hematopoietic stem cell transplantation (HSCT).
• 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:
  • 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.
  • 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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  • Cardiac: Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; no significant ECG abnormalities.
  • Renal: Serum creatinine ≤2.0×ULN.
  • Hepatic: ALT/AST ≤3.0×ULN (≤5.0×ULN if liver involvement); total bilirubin ≤2.0×ULN.
  • 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.