Study summary
1. Study Title:
A Study on the Efficacy and safety of Autocrine p40-Expressing CD19-Targeted Chimeric Antigen Receptor T Cells (CD19-CAR.p40-T) in Patients With Relapsed/Refractory CD19-Positive Hematologic Malignancies
2. Study Objectives:
2.1.1 Primary Objective To evaluate the safety of autocrine p40-expressing CD19-targeted chimeric antigen receptor T cells (CD19-CAR.p40-T) in the treatment of patients with relapsed/refractory CD19-positive hematologic malignancies.
2.1.2 Secondary Objective To evaluate the efficacy of autocrine p40-expressing CD19-targeted chimeric antigen receptor T cells (CD19-CAR.p40-T) in the treatment of patients with relapsed/refractory CD19-positive hematologic malignancies.
2.1.3 Exploratory Objective To evaluate the in vivo expansion and persistence of CD19-CAR.p40-T cells.
3. Participant Intervention:
Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19-CAR.p40-T cell infusion. The CD19-CAR.p40-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.
Eligibility criteria
Inclusion Criteria
Subjects must meet all of the following criteria to be enrolled:
1. • Aged 18 to 75 years, male or female;
2. • Histologically or cytologically diagnosed with relapsed/refractory CD19-positive hematologic malignancy according to the 2022 World Health Organization (WHO) diagnostic criteria;
3. • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
4. • Life expectancy of at least 3 months;
5. • No contraindications to peripheral blood leukapheresis;
6. • CD19 expression on tumor cells confirmed by flow cytometry and/or immunohistochemistry;
7. • No severe cardiac, pulmonary, hepatic, or renal dysfunction;
8. • Able to understand and willing to provide written informed consent. Exclusion Criteria
Subjects who meet any of the following criteria should be excluded from enrollment:
1. History of allergy to any component of the cellular product;
2. Complete blood count meeting any of the following criteria: white blood cell count (WBC) ≤1 × 10⁹/L, absolute neutrophil count (ANC) ≤0.5 × 10⁹/L, absolute lymphocyte count (ALC) ≤0.5 × 10⁹/L, or platelet count (PLT) ≤25 × 10⁹/L;
3. Laboratory abnormalities including, but not limited to, serum total bilirubin ≥1.5 mg/dL; serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times the upper limit of normal; or serum creatinine ≥2.0 mg/dL;
4. Class III or IV cardiac insufficiency according to the New York Heart Association (NYHA) functional classification, or left ventricular ejection fraction (LVEF) \<50% by echocardiography;
5. Abnormal pulmonary function, with oxygen saturation \<92% on room air;
6. History of myocardial infarction, cardiac angioplasty or stent placement, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;
7. Grade 3 hypertension with poor blood pressure control despite medication;
8. History of traumatic brain injury, disturbance of consciousness, epilepsy, severe cerebral ischemia, or cerebral hemorrhagic disease;
9. Autoimmune disease, immunodeficiency, or other conditions requiring treatment with immunosuppressive agents;
10. Uncontrolled active infection;
11. Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;
12. Receipt of a live vaccine within 4 weeks prior to enrollment;
13. Positive test results for HIV, HBV, HCV, or TPPA/RPR, or HBV carrier status;
14. History of alcohol abuse, drug abuse, or psychiatric illness;
15. Participation in any other clinical study within 3 months prior to enrollment in this clinical study;
16. Female subjects who meet any of the following conditions:
1. Pregnant or breastfeeding;
2. Planning to become pregnant during the study; or
3. Of childbearing potential and unwilling or unable to use effective contraception;
17. Any other condition that, in the investigator's opinion, makes the subject unsuitable for participation in this study.