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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory B-cell Lymphomas
• Intervention / Treatment: Drug: L218CAR19

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yanyan Liu; Phone Number: 86 037165587791; Email: yyliu@zzu.edu.cn
• Study Contact Backup: Name: Zheng Yan; Phone Number: 86 13598097015; Email: zlyyyanzheng3920@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Affiliated Cancer Hospital of Zhengzhou University
      • Contact: Yanyan Liu; Phone Number: 86-037165587791; Email: yyliu@zzu.edu.cn
      • Contact: Zheng Yan; Phone Number: 86+13598097015; Email: zlyyyanzheng3920@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; L218CAR19 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD)	Drug: L218CAR19; L218CAR19 is intravenously administered at three dose levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Occurrence of DLTs	Up to 4 weeks
Treatment-emergent adverse event (AE)	Incidence of treatment-emergent AEs	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of L218CAR19 in peripheral blood	To quantify L218CAR19 in a patient's peripheral blood at different time points	Up to 1 year
Time to reach Cmax (Tmax) of L218CAR19	To identify the time point when the concentration of L218CAR19 reaches maximum in a patient's peripheral blood	Up to 3 months
Area under the curve (AUC) of L218CAR19	To quantify the cumulative amount of L218CAR19 in a patient's peripheral blood over time	Up to 3 months
Clearance (CL) of L218CAR19	To determine the clearance factor of L218CAR19 in a patient's peripheral blood	Up to 3 months
Immunogenic response to L218CAR19	To evaluate the anti-drug antibodies in response to L218CAR19 administration in a patient's peripheral blood	Up to 1 year
Serum cytokine concentrations	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	Up to 3 months
ORR	To determine the overall (best) objective anti-cancer response by Lugano criteria	Up to 1 year
PFS	To evaluate the duration of patient's progression-free survival	Up to 1 year
OS	To evaluate the overall duration of patient's survival	Up to 1 year

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Yanyan Liu, Affiliated Cancer Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 16, 2024
• First Submitted That Met QC Criteria: June 22, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 22, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: HNSZLYYML09

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No