L218CAR19 in Patients With Relapsed/Refractory B-cell Lymphoma

A Phase 1, Open-label, Dose Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of L218CAR19 in Patients With CD19 Positive Relapsed/Refractory B-cell Lymphomas

L218CAR19 is a kind of chimeric antigen receptor T-cell immunotherapy targeting CD19 on B cells. The goal of this study is to determine the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of L218CAR19 in patients with B-cell lymphomas who have received at least two lines of systemic treatment.

Inclusion Criteria:

• Age 18-75 years at the time of inclusion
• Written informed consent
• Patients with relapsed/refractory CD19 positive B-cell lymphomas, who have received at least two lines of treatment
• With measurable disease
• ECOG PS 0-2 at protocol entry
• Estimated life expectancy of 3 months or longer
• Hemoglobin ≥ 8 g/dL (≥5 mmol/l); Platelets ≥ 75 x 10E9/L; Absolute neutrophil count ≥ 1.0 x 10E9/L; Platelets ≥ 50 x 10E9/L permitted if documented bone marrow involvement; Serum bilirubin ≤ 1.5 x upper limit of normal (ULN), or ≤3 x ULN if elevation is due to hepatic involvement by lymphoma; Serum glutamic-oxaloacetic transaminase (AST) and/or serum glutamic-pyruvic transaminase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if elevation is due to hepatic involvement by lymphoma; Serum creatinine ≤ 1.5 x ULNb; left ventricular ejection fraction (LVEF) ≥ 50%
• Women of childbearing potential must use safe anticonception (e.g. contraceptive pills, intrauterine devices etc.) during the study and 6 months after the administration of study drug; Male patients must use contraception for the duration of the study and 6 months after the administration of study drug if his partner is of childbearing potential

Exclusion Criteria:

• Patients with heart disease: atrial fibrillation; History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial infarction or other significant cardiac disease within 12 months of screening; LVEF<50%; clinical significant pericardial effusion; Long QT syndrome
• History of severe pulmonary function impairment
• With other uncontrolled malignancy
• With active bacterial, viral, or fungal infections
• WIth uncontrolled autoimmune disease or congential immunodeficiency
• HIV antibody positive patients
• Known severe hypersensitivity to biological product
• Patients with known active central nervous system (CNS) disease, including lymphoma CNS involvement
• Patients with prior CAR-T therapy
• History of allogeneic stem cell transplantation
• History of autogeneic stem cell transplantation within 6 months of screening
• History of major surgery within 4 weeks of screening
• Patients receiving live (attenuated) vaccines within 6 weeks of screening
• Pregnant or lactating women, or pregnant plan within 12 months
• Involvement of cardiac tissue by lymphoma
• with emergency due to oncothlipsis
• Unwillingness or inability to comply with the protocol
• Deemed 'unfit' by the treating physician