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

Official title

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

Overview

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

Detailed description

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.

Interventions

• Drug CD19 CAR-T cells
  Each subject receive CD19 CAR T-cells by intravenous infusion

Primary outcome measures

• Complete remission rate after CD19 CAR-T cell therapy [Time frame: 3 months after CD19 CAR-T cell therapy]

Secondary outcome measures (5)

• Overall response rate (ORR) [Time frame: After ZR2, 3 months after CAR-T cell therapy]
• Overall survival (OS) [Time frame: Up to 2 years after CD19 CAR-T cells infusion]
• Progression-free survival (PFS) [Time frame: Up to 2 years after CD19 CAR-T cells infusion]
• Duration of response (DOR) [Time frame: Up to 2 years after CD19 CAR-T cells infusion]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 2 years after CD19 targeted CAR T-cells infusion]

Eligibility criteria

Inclusion criteria

• Age no less than 18, no gender limit;
• 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;
• Confirmed CD19 and CD20 postive expressions in lymphoma cells
• ECOG score 0-2;
• Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
• Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
• No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
• Estimated survival time ≥ 3 months;
• Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion criteria

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

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital，College of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT04661020 · CD19-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗