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

Sponsor

Zhejiang University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04661020

Collaborator

Yake Biotechnology Ltd. (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Non-hodgkin Lymphoma,B Cell	Drug: CD19 CAR-T cells	Early Phase 1

Detailed Description

This is a single arm, open-label, single-center study. This study is indicated for elderly 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 20, 2020

Anticipated Primary Completion Date :

Dec 20, 2023

Anticipated Study Completion Date :

Dec 20, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Administration of CD19 CAR T-cells	Drug: CD19 CAR-T cells Each subject receive CD19 CAR T-cells by intravenous infusion Other Names: CD19 CAR-T cells injection

Arm

Intervention/Treatment

Experimental: Administration of CD19 CAR T-cells

Drug: CD19 CAR-T cells

Each subject receive CD19 CAR T-cells by intravenous infusion

Other Names:

CD19 CAR-T cells injection

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

B-cell Non-Hodgkin's Lymphoma (B-NHL), Overall response rate (ORR) [At Month 1, 3, 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
B-NHL, Overall survival (OS) [Up to 2 years after CD19 CAR-T cells infusion]
From the first infusion of CD19 CAR-T cells to death or the last visit
B-NHL, Event-free survival (EFS) [Up to 2 years after CD19 CAR-T cells infusion]
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
Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30) [At Baseline, Month 1, 3, 6, 9 and 12]
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
Activities of Daily Living (ADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
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
Instrumental Activities of Daily Living (IADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
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
Hospital Anxiety and Depression Scale (HADS) score [At Baseline, Month 1, 3, 6, 9 and 12]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age no less than 60, no gender limit;
Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
Newly diagnosed B-NHL, unwilling to receive first- or second-line chemotherapy, but willing to receive targeted drugs (such as CD20 monoclonal antibody，lenalidomide and Brutons tyrosine kinase inhibitor) as preconditioning regimens for CAR-T cell therapy;
At least one assessable tumor lesion per Lugano 2014 criteria
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.