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L218CAR19 in Patients With Relapsed/Refractory B-cell Lymphoma

Phase 1
Recruiting
Conditions
Relapsed/Refractory B-cell Lymphomas
Interventions
Registration Number
NCT06478381
Lead Sponsor
Henan Cancer Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
22
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Dose EscalationL218CAR19L218CAR19 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD)
Primary Outcome Measures
NameTimeMethod
Treatment-emergent adverse event (AE)Up to 1 year

Incidence of treatment-emergent AEs

Dose limiting toxicity (DLT)Up to 4 weeks

Occurrence of DLTs

Secondary Outcome Measures
NameTimeMethod
Quantification of L218CAR19 in peripheral bloodUp to 1 year

To quantify L218CAR19 in a patient's peripheral blood at different time points

Clearance (CL) of L218CAR19Up to 3 months

To determine the clearance factor of L218CAR19 in a patient's peripheral blood

Immunogenic response to L218CAR19Up to 1 year

To evaluate the anti-drug antibodies in response to L218CAR19 administration in a patient's peripheral blood

Serum cytokine concentrationsUp to 3 months

To measure the cytokine levels (e.g. TNFa, IL-6, IL-1, IL-2, etc.) in a patient's peripheral blood at different time points

Area under the curve (AUC) of L218CAR19Up to 3 months

To quantify the cumulative amount of L218CAR19 in a patient's peripheral blood over time

Time to reach Cmax (Tmax) of L218CAR19Up to 3 months

To identify the time point when the concentration of L218CAR19 reaches maximum in a patient's peripheral blood

ORRUp to 1 year

To determine the overall (best) objective anti-cancer response by Lugano criteria

PFSUp to 1 year

To evaluate the duration of patient's progression-free survival

OSUp to 1 year

To evaluate the overall duration of patient's survival

Trial Locations

Locations (1)

Affiliated Cancer Hospital of Zhengzhou University

🇨🇳

Zhengzhou, Henan, China

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