Refractory/relapsed T-lymphoblastic leukemia/lymphoma (T-ALL /LBL)
Conditions
Interventions
Low dose group:CXCR4 CCR9 CAR-T(U69): 1×10^6 CAR+T cells /kg
Middle dose group:CXCR4 CCR9 CAR-T(U69): 3×10^6 CAR+T cells /kg
High dose group:CXCR4 CCR9 CAR-T(U69): 6×10^6 CAR+T cells /kg
Sponsors
The First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Age
15 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for the study: 1. Voluntary provision of written informed consent and anticipated ability to complete all required study procedures and follow-up assessments; 2. >=15 and =5% blasts in bone marrow or peripheral blood at screening; Relapse: Defined as recurrence of blasts (>=5%) in peripheral blood or bone marrow or emergence of extramedullary disease after prior achievement of complete remission (CR/CRi). This includes early relapse (within 12 months of first remission), late relapse (>=12 months) failing to achieve remission after one multi-agent re-induction chemotherapy cycle, or relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT); Refractory: Defined as failure to achieve CR after at least two cycles of induction chemotherapy, or failure to achieve CR after one cycle of salvage therapy following relapse; 3.2 Relapsed/refractory For T-LBL: Presence of at least one measurable lesion at screening, defined as a nodal lesion with a long axis >15 mm or an extranodal lesion with a long axis >10 mm, as assessed by CT or MRI per the 2014 Lugano criteria; Relapsed/Refractory: Defined as relapse or disease progression after at least two prior lines of therapy; primary refractory disease (failure to achieve at least a partial response, PR, after first-line therapy); or relapse/progression after autologous or allogeneic HSCT (must be confirmed by tissue biopsy); 4. Confirmed CCR9 positivity on tumor cells via flow cytometry of bone marrow samples and/or via immunohistochemistry of extramedullary lesion biopsies at screening; 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; 6. Estimated life expectancy of greater than 3 months; 7. Adequate bone marrow reserve at screening, defined as: Absolute Neutrophil Count (ANC) >= 1.0 × 10^9/L; Absolute Lymphocyte Count (ALC) >= 0.3 × 10^9/L; Platelet Count (PLT) >= 20 × 10^9/L (transfusion support is permitted); 8. Organ Function: Adequate organ function defined as: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 50 mL/min (calculated by the Cockcroft-Gault formula); Left Ventricular Ejection Fraction (LVEF) >= 45%; Oxygen saturation >= 92% on room air; 9. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective contraception for at least one year post-infusion. Male subjects with female partners of childbearing potential must agree to use barrier contraception and refrain from sperm donation for at least one year post-infusion; 10. Must have adequate venous access for leukapheresis or venous blood draw and no other contraindications to leukapheresis.
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if they meet any of the following criteria: 1. Diagnosis of any other malignancy within 3 years prior to screening, except for those who have completed curative therapy and achieved over 3 years of disease-free survival with a low risk of recurrence as determined by the investigator (e.g., carcinoma in situ of the lung, basal cell carcinoma of the skin); 2. History or presence of central nervous system (CNS) disorders unrelated to the disease under study at screening or previously, such as seizure, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the CNS; 3. Prior receipt of cell therapies targeting CCR9, including but not limited to CAR-T cells; 4. Significant or active parenchymal CNS or cranial nerve lesions where, in the investigator’s judgment, the risks outweigh the benefits; 5. Systemic corticosteroid use discontinued 480 ms (calculated using Fridericia’s formula) at screening; or uncontrolled hypertension (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg) or pulmonary hypertension despite standard treatment; 11. Unstable systemic diseases per investigator judgment, including but not limited to severe hepatic, renal, or metabolic diseases requiring pharmacological intervention; 12. Active or uncontrolled autoimmune disease, or primary/secondary immunodeficiency; 13. History of severe immediate hypersensitivity to any drug used in the study; 14. Administration of any live vaccine within 6 weeks prior to screening; 15. Pregnant or lactating individuals; 16. History of autoimmune disease requiring systemic immunosuppressive or disease-modifying medication within the past 2 years (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus); 17. Allogeneic hematopoietic stem cell transplantation within 12 weeks prior to apheresis; presence of acute or moderate-to-severe chronic GVHD within 4 weeks prior to screening; or any systemic GVHD treatment within 4 weeks prior to cell infusion, including those requiring concomitant corticosteroid use; 18. Participation in any other interventional clinical trial within 4 weeks prior to screening; 19. Inability to comply with study procedur
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limited toxicity(DLT);adverse event;Recommended dose for Phase II(RP2D); | — |
Secondary
| Measure | Time frame |
|---|---|
| objective remission rate;Negative rate of minimal residual disease (MRD) (T-ALL);Duration of relief(DOR);Progression-free survival (PFS) / Relapse-free survival (RFS);Event-free survival period(EFS);overall survival(OS);Pharmacokinetics;Pharmacodynamics; | — |
Countries
China
Contacts
Public ContactShengLi Xue; Yang Xu
The First Affiliated Hospital of Soochow University
Outcome results
None listed