Overview
- 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.
Description
CD19-directed CAR-T cell therapy has demonstrated significant antitumor activity in B-cell hematologic malignancies; however, relapse, insufficient persistence, and limited durability of response remain important clinical challenges. CD19-CAR.p40-T is a genetically modified autologous T-cell product designed to target CD19-positive malignant cells while incorporating autocrine p40 expression, with the aim of enhancing T-cell expansion, persistence, and antitumor activity in vivo.
This study is a prospective, single-arm, Phase I/II clinical trial in patients with relapsed or refractory CD19-positive hematologic malignancies. After screening and leukapheresis, eligible participants will undergo manufacture of autologous CD19-CAR.p40-T cells. Before infusion, participants will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide to promote in vivo expansion and activity of the infused CAR-T cells. CD19-CAR.p40-T cells will then be administered as a single intravenous infusion.
Following infusion, participants will undergo close safety monitoring, including evaluation for cytokine release syndrome, immune effector cell-associated neurotoxicity, hematologic toxicity, infections, and other treatment-emergent adverse events. Disease assessments will be performed according to applicable disease-specific response criteria. In addition, serial blood samples will be collected to characterize the pharmacokinetic and cellular kinetic profile of CD19-CAR.p40-T cells, including expansion and persistence over time.
The purpose of this study is to characterize the safety profile of CD19-CAR.p40-T, evaluate its preliminary antitumor activity, and generate clinical and translational data to support further development of this investigational cell therapy in CD19-positive hematologic malignancies.
Eligibility
Inclusion Criteria
Subjects must meet all of the following criteria to be enrolled:
- • Aged 18 to 75 years, male or female;
- • Histologically or cytologically diagnosed with relapsed/refractory CD19-positive hematologic malignancy according to the 2022 World Health Organization (WHO) diagnostic criteria;
- • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- • Life expectancy of at least 3 months;
- • No contraindications to peripheral blood leukapheresis;
- • CD19 expression on tumor cells confirmed by flow cytometry and/or immunohistochemistry;
- • No severe cardiac, pulmonary, hepatic, or renal dysfunction;
- • 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:
- History of allergy to any component of the cellular product;
- 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;
- 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;
- 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;
- Abnormal pulmonary function, with oxygen saturation \<92% on room air;
- History of myocardial infarction, cardiac angioplasty or stent placement, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;
- Grade 3 hypertension with poor blood pressure control despite medication;
- History of traumatic brain injury, disturbance of consciousness, epilepsy, severe cerebral ischemia, or cerebral hemorrhagic disease;
- Autoimmune disease, immunodeficiency, or other conditions requiring treatment with immunosuppressive agents;
- Uncontrolled active infection;
- Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;
- Receipt of a live vaccine within 4 weeks prior to enrollment;
- Positive test results for HIV, HBV, HCV, or TPPA/RPR, or HBV carrier status;
- History of alcohol abuse, drug abuse, or psychiatric illness;
- Participation in any other clinical study within 3 months prior to enrollment in this clinical study;
- Female subjects who meet any of the following conditions:
- Pregnant or breastfeeding;
- Planning to become pregnant during the study; or
- Of childbearing potential and unwilling or unable to use effective contraception;
- Any other condition that, in the investigator's opinion, makes the subject unsuitable for participation in this study.
