CD19-targeted CAR-T cells that make p40 for relapsed or refractory CD19-positive blood cancers

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

This trial will try a patient's own CD19-directed CAR-T cells engineered to produce p40 to see if they work better and last longer in adults with relapsed or refractory CD19-positive blood cancers.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shenzhen University General Hospital (Academic / other)
• Drugs / interventions: CAR-T, Chimeric Antigen Receptor, chemotherapy, Cyclophosphamide, Fludarabine
• Locations: 1 site (Shenzhen, Other (Non U.s.))
• Trial ID: NCT07584889 on ClinicalTrials.gov

What this trial studies

This is a single-arm Phase 1/2 trial testing an autologous CD19-directed CAR-T product engineered to express autocrine p40 to enhance expansion and persistence. Eligible patients undergo leukapheresis for manufacture of CD19-CAR.p40-T cells, receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, and then a single intravenous CAR-T infusion. Participants are closely monitored for safety including cytokine release syndrome and neurotoxicity, and disease response is measured using standard disease-specific criteria. Serial blood samples will track CAR-T cell expansion, persistence, and pharmacokinetic/cellular-kinetic profiles.

Who should consider this trial

Good fit: Adults aged 18–75 with relapsed or refractory CD19-positive hematologic malignancies, ECOG performance status 0–2, confirmed CD19 expression, adequate organ function, and ability to undergo leukapheresis are the intended candidates.

Not a fit: Patients with CD19-negative disease, severe organ dysfunction, uncontrolled infection, a history of allergy to product components, or other exclusion criteria (for example very low WBC) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could improve CAR-T cell persistence and increase the durability of remissions for people with relapsed or refractory CD19-positive hematologic cancers.

How similar studies have performed: CD19-directed CAR-T therapies have produced strong responses in B-cell malignancies, but the autocrine p40 modification is a novel strategy with limited prior clinical data.

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.

Where this trial is running

Shenzhen, Other (Non U.s.)

• Shenzhen University General Hospital — Shenzhen, Other (Non U.s.), China (Recruiting)

Study contacts

• Principal investigator: lixin wang, PHD — Shenzhen University General Hospital
• Study coordinator: lixin wang, PHD

Conditions B Cell Lymphoma; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia