clinical trial of cd5-targeted car-nk therapy for relapse/refractory t-cell hematologic malignancies

Conditions: T-ALL/Lymphoma

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.

this study is a single-arm, open-label, dose-finding and expansion clinical trial aimed at evaluating the safety and efficacy of anti-cd5 car-nk therapy for the treatment of patients with relapsed/refractory t-cell hematologic malignancies. the goal is to determine the recommended dose of car-nk cell therapy for these conditions. the study includes three dose groups: 1×10⁷ car-positive cells/kg, 3×10⁷ car-positive cells/kg, and 5×10⁷ car-positive cells/kg. 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. the investigaors have the flexibility to adjust the second infusion dose based on the subject's condition.

Eligibility criteria:
inclusion criteria: - 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: 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.

Keywords: t-all t-lbl ptcl-nos aitl alcl enkl t-pll atll mf/ss