CD19 CAR-T Therapy for Patients With Newly Diagnosed High-risk Large B-cell Lymphoma

Clinical Trial for the Efficacy and Safety of CD19 CAR-T Therapy for Patients With Newly Diagnosed High-risk Large B-cell Lymphoma

A Study of CD19 CAR-T Therapy for Patients With Newly Diagnosed High-risk Large B-cell Lymphoma

This study is indicated for patients with CD19+ newly diagnosed high-risk large B-cell lymphoma. This study is an investigator-initiated, single-center, single-arm phase II clinical trial of rituximab, lenalidomide, and zanubrutinib (ZR2) with Sequential CAR-T cell as first-line therapy for newly diagnosed high-risk LBCL. Primary objective is to explore the efficacy and also safety.

Inclusion Criteria:

1. Age no less than 18, no gender limit;
2. Newly diagnosed high-risk Large B-cell Lymphoma, which was defined by the following criteria: (1) DLBCL not otherwise specified with an IPI score ≥3 at diagnosis, (2) high grade B-cell lymphoma (HGBL) with gene rearrangement of MYC and BCL2 and/or BCL6, (3) HGBL not otherwise specified;
3. Confirmed CD19 and CD20 postive expressions in lymphoma cells
4. ECOG score 0-2;
5. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
6. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
7. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
8. Estimated survival time ≥ 3 months;
9. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

1. Central nervous system involvement by lymphoma；History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
4. Active infection of hepatitis B virus or hepatitis C virus;
5. Previously treated with any CAR-T cell product or other genetically modified T cell therapies;
6. Insufficient amplification capacity in response to CD3/CD28 co-stimulus signal (<5 times) ;
7. Other uncontrolled diseases that were not suitable for this trial;
8. Patients with HIV infection;
9. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.