Relapsed/Refractory B-cell Lymphomas
Conditions
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.
Interventions
DRUGL218CAR19
L218CAR19 is intravenously administered at three dose levels.
Sponsors
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT) | Up to 4 weeks | Occurrence of DLTs |
| Treatment-emergent adverse event (AE) | Up to 1 year | Incidence of treatment-emergent AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve (AUC) of L218CAR19 | Up to 3 months | To quantify the cumulative amount of L218CAR19 in a patient's peripheral blood over time |
| Clearance (CL) of L218CAR19 | Up to 3 months | To determine the clearance factor of L218CAR19 in a patient's peripheral blood |
| Immunogenic response to L218CAR19 | Up to 1 year | To evaluate the anti-drug antibodies in response to L218CAR19 administration in a patient's peripheral blood |
| Quantification of L218CAR19 in peripheral blood | Up to 1 year | To quantify L218CAR19 in a patient's peripheral blood at different time points |
| ORR | Up to 1 year | To determine the overall (best) objective anti-cancer response by Lugano criteria |
| PFS | Up to 1 year | To evaluate the duration of patient's progression-free survival |
| OS | Up to 1 year | To evaluate the overall duration of patient's survival |
| Serum cytokine concentrations | Up 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 |
| Time to reach Cmax (Tmax) of L218CAR19 | Up to 3 months | To identify the time point when the concentration of L218CAR19 reaches maximum in a patient's peripheral blood |
Countries
China
Contacts
Primary ContactYanyan Liu
Backup ContactZheng Yan
Outcome results
None listed