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CD19 CAR-T Expressing IL-7 and CCL19 Combined With Anti-PD1 in RR-DLBCL

Primary Purpose

Diffuse Large B-cell Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19-7×19 CAR-T combined with Tislelizumab
Sponsored by
Ningbo No. 1 Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18, upper limit 75, male or female; ECOG score 0-3; Histologically confirmed diffuse large B-cell lymphoma (DLBCL) [diagnostic criteria according to WHO 2008]; CD19 positive (immunohistochemistry or flow cytometry). DLBCL refractory or relapse is defined as: complete remission is not achieved after 2-line treatment; let What disease progress occurs during treatment, or the disease stability time is equal to or less than 6 months; Or autologous hematopoietic stem Disease progression or recurrence within 12 months after cell transplantation; Previous treatment for patients with diffuse large B cell lymphoma must include rituximab (CD20 monoclonal antibody) and anthracyclines; At least one measurable lesion is required, and any lymph node lesion with a length greater than 1.5cm or extranodal lesion is required If any length diameter is greater than 1.0 cm, the lesions on PET-CT scan have uptake (SUV is larger than liver blood pool); Absolute value of peripheral blood neutrophils ≥ 1000/ μ l. Platelets ≥ 45000/ μ l Heart, liver and kidney functions: creatinine < 1.5mg/dL; ALT/AST Less than 2.5 times of normal upper limit; Total bilirubin < 1.5mg/dL; Cardiac ejection fraction (EF) ≥ 50%; Have sufficient understanding and voluntarily sign the informed consent form; People with fertility must be willing to use contraceptive methods; According to the judgment of the researcher, the expected survival period is at least 4 months; Willing to follow the visit schedule, administration plan, laboratory inspection and other test steps. Exclusion Criteria: Have a history of other tumors; Autologous hematopoietic stem cell transplantation was performed within 6 weeks; Any target CAR-T treatment was performed within 3 months before this CAR-T treatment; Previously used any commercially available PD-1 monoclonal antibody; Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection; Active autoimmune diseases; Uncontrollable active bacterial and fungal infections; HIV infection and syphilis infection; Active hepatitis B or hepatitis C: hepatitis B: HBV-DNA ≥ 1000 IU/mL; Hepatitis C: HCV RNA is positive and liver function is abnormal. Known central nervous system lymphoma.

Sites / Locations

  • The Second Affiliated Hospital of Zhejiang University, Ningbo First HospitalRecruiting
  • Ningbo First HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T combined with anti-PD1 treatment group

Arm Description

CD19-7×19 CAR-T combined with Tislelizumab

Outcomes

Primary Outcome Measures

Adverse events profile
Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated.
Objective Response Rate
Proportion of CR and PR subjects will be assessed at 3 months post-infusion.

Secondary Outcome Measures

Progress free survival time
To measure the duration of response over a follow-up period of 24 months.
Overall survival
OS will be assessed from the first chimeric antigen receptor T cells (CAR-T) given to death or last follow-up.

Full Information

First Posted
November 26, 2022
Last Updated
December 12, 2022
Sponsor
Ningbo No. 1 Hospital
Collaborators
Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05659628
Brief Title
CD19 CAR-T Expressing IL-7 and CCL19 Combined With Anti-PD1 in RR-DLBCL
Official Title
Phase Ib Clinical Study of CD19 CAR-T Expressing IL-7 and CCL19 Combined With Tislelizumab in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ningbo No. 1 Hospital
Collaborators
Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The goal of this clinical trial is to test CD19-7×19 CAR-T cells combined with Tislelizumab in refractory and relapsed diffuse large B lymphoma. The main question[s] it aims to answer are: question 1:What is the safety of CD19-7×19 CAR-T cells combined with Tislelizumab in the treatment of relapsed or refractory diffuse large B-cell lymphoma. question 2:What is the efficacy of CD19-7×19 CAR-T cells combined with Tislelizumab in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Participants will be asked to receive clinical evaluation before CAR-T, including physical examination, blood routine test, biochemical test, imaging test, etc.Peripheral blood lymphocytes will be collected for preparation of CAR-T cells after enrollment. Pretreatment chemotherapy with fludarabine and cyclophosphamide will be used before CAR-T infusion. On the 31st day after CAR-T infusion, Tislelizumab 200mg was given once every 21 days for 6 cycles. Participants will be required to report concomitant medication and adverse events, and their disease was evaluated throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-T combined with anti-PD1 treatment group
Arm Type
Experimental
Arm Description
CD19-7×19 CAR-T combined with Tislelizumab
Intervention Type
Combination Product
Intervention Name(s)
CD19-7×19 CAR-T combined with Tislelizumab
Intervention Description
Participants will receive 2×106/Kg CD19-7×19 CAR-T cells infusion and Tislelizumab 200mg every 21 days for 6 cycle on the 31st day after CAR-T infusion.
Primary Outcome Measure Information:
Title
Adverse events profile
Description
Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated.
Time Frame
Measured from start of treatment until 28 days after last dose.
Title
Objective Response Rate
Description
Proportion of CR and PR subjects will be assessed at 3 months post-infusion.
Time Frame
up to 3 months
Secondary Outcome Measure Information:
Title
Progress free survival time
Description
To measure the duration of response over a follow-up period of 24 months.
Time Frame
up to 24 months
Title
Overall survival
Description
OS will be assessed from the first chimeric antigen receptor T cells (CAR-T) given to death or last follow-up.
Time Frame
up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18, upper limit 75, male or female; ECOG score 0-3; Histologically confirmed diffuse large B-cell lymphoma (DLBCL) [diagnostic criteria according to WHO 2008]; CD19 positive (immunohistochemistry or flow cytometry). DLBCL refractory or relapse is defined as: complete remission is not achieved after 2-line treatment; let What disease progress occurs during treatment, or the disease stability time is equal to or less than 6 months; Or autologous hematopoietic stem Disease progression or recurrence within 12 months after cell transplantation; Previous treatment for patients with diffuse large B cell lymphoma must include rituximab (CD20 monoclonal antibody) and anthracyclines; At least one measurable lesion is required, and any lymph node lesion with a length greater than 1.5cm or extranodal lesion is required If any length diameter is greater than 1.0 cm, the lesions on PET-CT scan have uptake (SUV is larger than liver blood pool); Absolute value of peripheral blood neutrophils ≥ 1000/ μ l. Platelets ≥ 45000/ μ l Heart, liver and kidney functions: creatinine < 1.5mg/dL; ALT/AST Less than 2.5 times of normal upper limit; Total bilirubin < 1.5mg/dL; Cardiac ejection fraction (EF) ≥ 50%; Have sufficient understanding and voluntarily sign the informed consent form; People with fertility must be willing to use contraceptive methods; According to the judgment of the researcher, the expected survival period is at least 4 months; Willing to follow the visit schedule, administration plan, laboratory inspection and other test steps. Exclusion Criteria: Have a history of other tumors; Autologous hematopoietic stem cell transplantation was performed within 6 weeks; Any target CAR-T treatment was performed within 3 months before this CAR-T treatment; Previously used any commercially available PD-1 monoclonal antibody; Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection; Active autoimmune diseases; Uncontrollable active bacterial and fungal infections; HIV infection and syphilis infection; Active hepatitis B or hepatitis C: hepatitis B: HBV-DNA ≥ 1000 IU/mL; Hepatitis C: HCV RNA is positive and liver function is abnormal. Known central nervous system lymphoma.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lixia Sheng, doctor
Phone
86-574-87085596
Email
slx800408@163.com
Facility Information:
Facility Name
The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenbin Qian, Doctor
Phone
86-571-87581969
Email
qianwb@zju.edu.cn
Facility Name
Ningbo First Hospital
City
Ningbo
State/Province
Zhejiang
ZIP/Postal Code
315010
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lixia Sheng, doctor
Phone
86-574-87085596
Email
slx800408@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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CD19 CAR-T Expressing IL-7 and CCL19 Combined With Anti-PD1 in RR-DLBCL

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