Back to resultsCD19 CAR-T Therapy for Elderly Patients With B-cell Non-Hodgkin's Lymphoma
Primary Purpose
Non-hodgkin Lymphoma,B Cell
Status
Not yet recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19 CAR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for Non-hodgkin Lymphoma,B Cell focused on measuring Non Hodgkin Lymphoma, CAR T-cell therapy, CD19
Eligibility Criteria
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.
Sites / Locations
- The First Affiliated Hospital，College of Medicine, Zhejiang University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Administration of CD19 CAR T-cells
Arm Description
Outcomes
Primary Outcome Measures
Dose-limiting toxicity (DLT)
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Secondary Outcome Measures
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
B-NHL, Overall survival (OS)
From the first infusion of CD19 CAR-T cells to death or the last visit
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
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
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
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
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
Full Information
NCT ID
NCT04661020
First Posted
December 3, 2020
Last Updated
December 3, 2020
Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04661020
Brief Title
CD19 CAR-T Therapy for Elderly Patients With B-cell Non-Hodgkin's Lymphoma
Official Title
Clinical Trial for the Safety and Efficacy of CD19 CAR-T Therapy for Elderly Patients With B-cell Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 20, 2020 (Anticipated)
Primary Completion Date
December 20, 2023 (Anticipated)
Study Completion Date
December 20, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Study of CD19 CAR-T Therapy for Elderly Patients With B-cell Non-Hodgkin's Lymphoma.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-hodgkin Lymphoma,B Cell
Keywords
Non Hodgkin Lymphoma, CAR T-cell therapy, CD19
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Administration of CD19 CAR T-cells
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CD19 CAR-T cells
Other Intervention Name(s)
CD19 CAR-T cells injection
Intervention Description
Each subject receive CD19 CAR T-cells by intravenous infusion
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Time Frame
Baseline up to 28 days after CD19 targeted CAR T-cells infusion
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Time Frame
Up to 2 years after CD19 targeted CAR T-cells infusion
Secondary Outcome Measure Information:
Title
B-cell Non-Hodgkin's Lymphoma (B-NHL), Overall response rate (ORR)
Description
Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
Time Frame
At Month 1, 3, 6, 12, 18 and 24
Title
B-NHL, Overall survival (OS)
Description
From the first infusion of CD19 CAR-T cells to death or the last visit
Time Frame
Up to 2 years after CD19 CAR-T cells infusion
Title
B-NHL, Event-free survival (EFS)
Description
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
Time Frame
Up to 2 years after CD19 CAR-T cells infusion
Title
Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30)
Description
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
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
Title
Activities of Daily Living (ADL) score
Description
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
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
Title
Instrumental Activities of Daily Living (IADL) score
Description
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
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
Title
Hospital Anxiety and Depression Scale (HADS) score
Description
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
Time Frame
At Baseline, Month 1, 3, 6, 9 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
He Huang, PhD
Phone
86-13605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongxian Hu, PhD
Phone
86-15957162012
Email
huyongxian2000@aliyun.com
Facility Information:
Facility Name
The First Affiliated Hospital，College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang, PhD
Phone
86-13605714822
Email
hehuangyu@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
CD19 CAR-T Therapy for Elderly Patients With B-cell Non-Hodgkin's Lymphoma
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