Efficacy and Safety of CD19-CAR.p40-T in Patients With Relapsed/Refractory CD19-Positive Hematologic Malignancies

Phase 2RecruitingNCT07584889

Shenzhen University General Hospital10 enrolled

Overview

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.

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

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

TEAEs

Treatment-emergent adverse events will be evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

Time frame: From date of initial treatment to the 30 days after treatment

Secondary Outcomes

Disease-related clinical responses

Best overall response will be evaluated using disease-specific response criteria applicable to the enrolled hematologic malignancy.

Time frame: From date of enrollment until the date of clinical responses,up to 2 years

Efficacy and Safety of CD19-CAR.p40-T in Patients With Relapsed/Refractory CD19-Positive Hematologic Malignancies

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts