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

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

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

Study Overview

• Status: Recruiting
• Conditions: Non-hodgkin Lymphoma,B Cell
• Intervention / Treatment: Drug: CD19 CAR-T cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: He Huang, PhD; Phone Number: 86-13605714822; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, PhD; Phone Number: 86-15957162012; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital，College of Medicine, Zhejiang University
      • Contact: He Huang, PhD; Phone Number: 86-13605714822; Email: hehuangyu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age no less than 18, no gender limit;
2. 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;
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;
4. Patients with PR or SD efficacy evaluated by PET-CT after two courses of tumor reduction therapy;
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. ECOG performance status 0 to 2;
10. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

1. 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. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
8. Other uncontrolled diseases that were not suitable for this trial;
9. Patients with HIV infection;
10. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: CAR T-cell therapy; CD19; Non Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CD19-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No