Efficacy and Safety of CD19/CD20 CAR/TRuC-T in Relapsed/Refractory B-Cell Lymphoma

Overview

1. Study Title: A Study on the Efficacy and safety of CD19/CD20 CAR/TRuC-T in Relapsed/Refractory B-Cell Lymphoma 2. Study Objectives: Primary Objective: To evaluate the safety of CD19/CD20 CAR/TRuC-T cell therapy in patients with relapsed/refractory B-cell lymphoma. Secondary Objective: To evaluate the efficacy of CD19/CD20 CAR/TRuC-T cell therapy in patients with relapsed/refractory B-cell lymphoma. Exploratory Objective: To assess in vivo expansion and persistence of infused CD19/CD20 CAR/TRuC-T cells. 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/TRuC-T cell infusion. The CAR/TRuC-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.

Detailed description

Detailed Description:

This is a prospective, interventional Phase I/II clinical study designed to evaluate the safety and efficacy of CD19/CD20 CAR/TRuC-T cell therapy in patients with relapsed/refractory B-cell lymphoma. A total of 20 patients aged 18-75 years with relapsed/refractory B-cell lymphoma will be enrolled. All patients must have histopathologically confirmed disease and positive CD20 expression in tumor tissue.

CD19/CD20 CAR/TRuC-T cells will be administered as a single intravenous infusion at a total dose of 0.5-2 × 10\^6 CAR-T cells/kg. Eligible subjects (N=20) will be assigned by the investigator to receive CD19/CD20 CAR/TRuC-T cell infusion.

Endpoints:

* Primary Endpoint:

o Incidence and severity of treatment-emergent adverse events (TEAEs) within 30 days after CD19/CD20 CAR/TRuC-T cell infusion. * Secondary Endpoints:

* Objective response rate (ORR = CR + PR) assessed within 8 weeks after infusion; * Overall survival (OS) and progression-free survival (PFS) at 6 months; * In vivo expansion and persistence kinetics of infused CD19/CD20 CAR/TRuC-T cells.

Interventions

• Combination product CAR/TRuC-T
  Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned CD19/CD20 CAR/TRuC-T cell infusion. The CAR/TRuC-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

Subjects must meet all of the following criteria to be enrolled:

• Aged 18 to 75 years, regardless of sex;
• Histologically confirmed relapsed/refractory B-cell lymphoma according to the 2020 World Health Organization (WHO) classification;
• ECOG performance status of 0-2;
• Expected survival of at least 3 months;
• CD20 expression on tumor cells confirmed by flow cytometry and/or immunohistochemistry;
• Patients who are resistant/refractory to CD19 CAR-T cell therapy or have low CD19 expression;
• No severe cardiac, pulmonary, hepatic, or renal disease;
• Able to understand and willing to sign the informed consent form for this study;
• No contraindications to peripheral blood mononuclear cell collection/apheresis;
• At least one measurable and evaluable lesion according to RECIST 1.1;
• Must have previously received standard first-line and second-line therapy;
• No antibody-based therapy within 2 weeks prior to cell therapy. Exclusion Criteria

Subjects meeting any of the following criteria will be excluded:

• History of allergy to any component of the cell product;
• Abnormal complete blood count meeting any of the following: WBC ≤1 × 10⁹/L, ANC ≤0.5 × 10⁹/L, ALC ≤0.5 × 10⁹/L, or PLT ≤25 × 10⁹/L;
• Laboratory abnormalities including, but not limited to, any of the following: total serum bilirubin ≥1.5 mg/dL; ALT or AST >2.5 times the upper limit of normal; serum creatinine ≥2.0 mg/dL;
• New York Heart Association (NYHA) Class III or IV heart failure, or left ventricular ejection fraction (LVEF) <50% on echocardiography;
• Abnormal pulmonary function, with oxygen saturation <92% on room air;
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;
• Grade 3 hypertension with poor blood pressure control despite medication;
• History of craniocerebral trauma, disturbance of consciousness, epilepsy, severe cerebral ischemia, or cerebral hemorrhagic disease;
• Presence of autoimmune disease, immunodeficiency, or other conditions requiring immunosuppressive therapy;
• Presence of uncontrolled active infection;
• Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;
• Receipt of a live vaccine within 4 weeks prior to enrollment;
• Positive for HIV, HBV, HCV, or TPPA/RPR, or HBV carrier status;
• History of alcohol abuse, drug abuse, or psychiatric illness;
• Participation in any other clinical study within 3 months prior to enrollment in this study;
• Female subjects meeting any of the following conditions:

• currently pregnant or breastfeeding;
• planning to become pregnant during the study period; or
• of childbearing potential and unwilling or unable to use effective contraception;
• Any other condition that, in the investigator's judgment, makes 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: NCT07508605 · 113 · 113

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗