Efficacy and Safety of CD19CD20-CAR.p40-T in B-cell Lymphoma

Official title

Study on the Efficacy and Safety of Autocrine p40 Chimeric Antigen Receptor T Cells Targeting CD19 and CD20 (CD19CD20-CAR.p40-T) in Refractory B-Cell Lymphoma

Overview

1. Study Title: A Study on the Efficacy and Safety of Autocrine p40 CD19/CD20 Dual-Targeting Chimeric Antigen Receptor T-Cells (CD19/CD20-CAR.p40-T) in Relapsed/Refractory B-Cell Lymphoma 2. Study Objectives: * Primary Objective: To evaluate the safety of CD19/CD20 dual-targeting CAR.p40-T cell therapy in patients with relapsed/refractory B-cell lymphoma. * Secondary Objective: To evaluate the efficacy of CD19/CD20 dual-targeting CAR.p40-T cell therapy in patients with relapsed/refractory B-cell lymphoma. 3. Participant Intervention: * Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19/CD20-CAR.p40-T cell infusion or CD19 CAR.p40-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

Detailed description

A prospective, interventional Phase I/IIa clinical study to evaluate the safety and efficacy of autocrine p40 CAR-T cells targeting dual CD19/CD20 in refractory/relapsed B-cell lymphoma. A total of 20 patients aged 18 to 75 years with pathologically confirmed B-cell lymphoma (refractory/relapsed) will be enrolled. The total dose of CAR-T cells is 0.5-2×10\^6 CAR-T cells/kg, administered as a single intravenous infusion. Eligible subjects (n=20) will be assigned by the investigator to receive either CD19CD20 CAR.p40-T injection or CD19 CAR.p40-T injection.

* Primary Endpoint\*\*: To assess treatment-emergent adverse events (TEAEs) within 30 days after intravenous infusion of CAR-T cells. * Secondary Endpoints\*\*:

* Objective response rate (ORR=CR+PR) within 8 weeks; * Overall survival (OS) and progression-free survival (PFS) at 6 months; * In vivo expansion and persistence kinetics of CAR-T cells.

Interventions

• Combination product CAR-T cell
  Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19/CD20-CAR.p40-T or CD19-CAR.p40-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

Primary outcome measures

• TEAEs [Time frame: From date of initial treatment to the 30 days after treatment]

Secondary outcome measures (1)

• Disease-related clinical responses [Time frame: From date of enrollment until the date of clinical responses,up to 2 years]

Eligibility criteria

Inclusion criteria

• Aged between 15 and 75 years old, regardless of gender;
• Diagnosed with relapsed/refractory B-cell lymphoma according to the 2020 World Health Organization (WHO) diagnostic criteria;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• Expected survival time of ≥ 3 months;
• Confirmation of CD20 expression in tumor cells by flow cytometry/immunohistochemistry;
• Patients tolerant to CD19 CAR-T cell therapy or those with low CD19 expression;
• No severe heart, lung, liver, or kidney diseases;
• Capable of understanding and willing to sign the informed consent form for this trial;
• No contraindications to peripheral blood apheresis for the subject;
• Having clearly measurable and evaluable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard;
• The subject must have received standard first- and second-line treatment regimens;
• Not having received antibody-based drug treatment within 2 weeks before cell therapy.

Exclusion criteria

• History of allergy to any component in the cell product;
• The following conditions in the blood routine examination: White blood cell count (WBC) ≤ 1×10⁹/L, absolute neutrophil count (ANC) ≤ 0.5×10⁹/L, absolute lymphocyte count (ALC) ≤ 0.5×10⁹/L, platelet count (PLT) ≤ 25×10⁹/L;
• The following conditions in laboratory tests: including but not limited to, total serum bilirubin ≥ 1.5 mg/dl; serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the upper limit of normal; serum creatinine ≥ 2.0 mg/dl;
• Patients with heart failure classified as grade III or IV according to the New York Heart Association (NYHA) classification criteria; or left ventricular ejection fraction (LVEF) < 50% as detected by echocardiography;
• Abnormal lung function with oxygen saturation < 92% under room air;
• Myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically severe heart diseases within 12 months before enrollment;
• Grade 3 hypertension with poorly controlled blood pressure despite drug treatment;
• History of craniocerebral trauma, disturbance of consciousness, epilepsy, severe cerebral ischemia or intracerebral hemorrhagic diseases;
• Patients with autoimmune diseases, immunodeficiency, or other conditions requiring immunosuppressive agent treatment;
• Presence of uncontrolled active infection;
• Previous use of any CAR-T cell product or other genetically modified T cell therapies;
• Vaccination with live vaccines within 4 weeks before enrollment;
• Subjects positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum particle agglutination assay (TPPA)/rapid plasma reagin (RPR), as well as HBV carriers;
• History of alcohol abuse, drug abuse, or mental illness in the subject;
• The subject participated in any other clinical study within 3 months before joining this clinical study;
• Female subjects with any of the following conditions: a) Currently pregnant or breastfeeding; or b) Having a pregnancy plan during the trial period; or c) Being fertile but unable to take effective contraceptive measures;
• Other circumstances that, in the opinion of the investigator, make the subject unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Health services research

Study locations

China · 1 center

• Shenzhen University General Hospital — Shenzhen

Identifiers

NCT: NCT07097207 · 111 · 111

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗