Clinical trial NCT06478381: L218CAR19 in Patients With Relapsed/Refractory B-cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory B-cell Lymphomas
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2024-06-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: Up to 4 weeks
measure: Treatment-emergent adverse event (AE)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Quantification of L218CAR19 in peripheral blood
timeFrame: Up to 1 year
measure: Time to reach Cmax (Tmax) of L218CAR19
timeFrame: Up to 3 months
measure: Area under the curve (AUC) of L218CAR19
timeFrame: Up to 3 months
measure: Clearance (CL) of L218CAR19
timeFrame: Up to 3 months
measure: Immunogenic response to L218CAR19
timeFrame: Up to 1 year
measure: Serum cytokine concentrations
timeFrame: Up to 3 months
measure: ORR
timeFrame: Up to 1 year
measure: PFS
timeFrame: Up to 1 year
measure: OS
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Affiliated Cancer Hospital of Zhengzhou University
state: Henan
Study officials:
affiliation: Affiliated Cancer Hospital of Zhengzhou University
name: Yanyan Liu
role: PRINCIPAL_INVESTIGATOR
References: