CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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A Study of CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma.

Detailed Description
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This is a single arm, open-label, single-center study. This study is indicated for patients with CD19+ non-Hodgkin's lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 36 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.

Official Title
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Clinical Trial for the Safety and Efficacy of CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma

Conditions
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Non-hodgkin Lymphoma,B Cell

Intervention / Treatment
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* Drug: CD19 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age no less than 18, no gender limit; Histologically confirmed diagnosis of HGBCL（HGBCL-NOS、HGBCL involving combined rearrangements of MYC, bcl-2 and bcl-6）DLBCL、not otherwise specified and IPI≥3; Newly diagnosed B-NHL, unwilling to receive RCHOP first- or second-line chemotherapy, but willing to receive targeted drugs (such as a regimen consisting of CD20 monoclonal antibody，lenalidomide and Brutons tyrosine kinase inhibitor for two courses) as preconditioning regimens for CAR-T cell therapy; Patients with PR or SD efficacy evaluated by PET-CT after two courses of tumor reduction therapy; 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; ECOG performance status 0 to 2; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: 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) ; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of CD19 CAR T-cells<br> | Drug: CD19 CAR-T cells<br>* Each subject receive CD19 CAR T-cells by intravenous infusion<br>* Other names: CD19 CAR-T cells injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD19 targeted CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after CD19 targeted CAR T-cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-cell Non-Hodgkin's Lymphoma (B-NHL), Overall response rate (ORR) | Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24 | At Month 1, 3, 6, 12, 18 and 24 | 
| B-NHL, Overall survival (OS) | From the first infusion of CD19 CAR-T cells to death or the last visit | Up to 2 years after CD19 CAR-T cells infusion | 
| B-NHL, Event-free survival (EFS) | From the first infusion of CD19 CAR-T cells to the occurrence of any event, including death, relapse or generelapse,disease progression (any one occurs first), and the last visit | Up to 2 years after CD19 CAR-T cells infusion | 
| Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30) | Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life QuestionnaireCore 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a betteroutcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of lifeat Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 
| Activities of Daily Living (ADL) score | Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scoresmean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 
| Instrumental Activities of Daily Living (IADL) score | Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean aworse outcome] at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 
| Hospital Anxiety and Depression Scale (HADS) score | Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean aworse outcome] at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non Hodgkin Lymphoma, CAR T-cell therapy, CD19