Brief Summary

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for 35% of lymphoma. Chimeric antigen receptor T cell (CAR-T) therapy is a new method to treat DLBCL. KTE-C19, published in the New England Medical Journal in December 2017, was used to treat relapsed and refractory B-cell lymphoma. One year of treatment for 111 patients, the total response rate was 82%, and the complete remission rate was 54%. However, a large number of clinical studies have shown that about 20% of patients with B-ALL and 50% of patients with B-NHL cannot achieve complete remission (CR) after CD19-CAR-T treatment. Targeting tumor microenvironment is an important new method to overcome the drug resistance of CAR-T cells. In this study, IL-7 and CCL19 were connected on the basis of traditional second generation CD19 CAR-T cells to construct novel fourth generation CAR-T cells, which can promote the infiltration, accumulation and survival of CAR-T cells in lymphoma tissue, and further enhance the anti-tumor effect of traditional CAR-T cells. At the same time, combined with four generations of CAR-T cells and PD1 monoclonal antibody, PD1 / PDL1 signal pathway was blocked, anti-tumor effect of CAR-T was improved, and immune response and long-term remission rate of DLBCL were improved.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

participants targeted

Target at P25-P50 for phase_1

Timeline

Completed

Started Jun 2020

Typical duration for phase_1

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.2 years study duration

First Submitted

Initial submission to the registry

May 6, 2020

Completed

5 days until next milestone

First Posted

Study publicly available on registry

May 11, 2020

Completed

1 month until next milestone

Study Start

First participant enrolled

June 18, 2020

Completed

3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2023

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2023

Completed

Last Updated

February 6, 2023

Status Verified

February 1, 2023

Enrollment Period

3.2 years

First QC Date

May 6, 2020

Last Update Submit

February 2, 2023

Conditions

Diffuse Large B-cell Lymphoma

Keywords

diffuse large B-cell lymphomaChimeric antigen receptor T cellPD1 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

Objective response rate
Objective response rate of the combination of CD19 CAR-T Expressing IL7 and CCL19 and PD1 mAb
3 months

Secondary Outcomes (4)

progression-free survival
2 years
overall survival
2 years
Duration of Overall Response
2 years
Relapse rate
2 years

Study Arms (1)

CD19-7×19 CAR-T plus PD1 monoclonal antibody

EXPERIMENTAL

Biological: CD19-7×19 CAR-T plus PD1 monoclonal antibody

Interventions

CD19-7×19 CAR-T plus PD1 monoclonal antibodyBIOLOGICAL

Three different doses of CD19-7×19 CAR-T (1×106/kg、2×106/kg、3×106/kg) plus 200mg Tislelizumab every 3 weeks for 6 times

CD19-7×19 CAR-T plus PD1 monoclonal antibody

Eligibility Criteria

Age18 Years - 75 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

(1) Age ≥ 18, upper limit 75, unlimited for men and women;
(2) ECOG score 0-3;
(3) Histologically confirmed diffuse large B-cell lymphoma (DLBCL) \[according to who 2008\];
(4) CD19 was positive (immunohistochemistry or flow cytometry).
(5) The definition of refractory or relapse of DLBCL is: no complete remission after 2-line treatment; disease progression in any treatment process, or disease stabilization time equal to or less than 6 months; or disease progression or relapse within 12 months after hematopoietic stem cell transplantation;
(6) The previous treatment of diffuse large B cell lymphoma must include rituximab (CD20 mAb) and anthracycline;
(7) There should be at least one measurable focus. It is required that any length of lymph node focus should be greater than 1.5cm or any length of extranodal focus should be greater than 1.0cm. PET-CT scan focuses should have uptake (SUV is greater than liver blood pool);
(8) The absolute value of neutrophils in peripheral blood ≥ 1000 / μ L, platelet ≥ 45000 / μ L;
(9) Heart, liver and kidney function: creatinine \< 1.5mg/dl; ALT (alanine aminotransferase) / AST (aspartate aminotransferase) 2.5 times lower than the normal upper limit; total bilirubin \< 1.5mg/dl; heart ejection fraction (EF) ≥ 50%;
(10) Sufficient understanding ability and voluntary signing of informed consent;
(11) Those with fertility must be willing to use contraceptive methods;
(12) According to the judgment of the researchers, the expected survival time is more than 4 months;
(13) Willing to follow visit schedule, administration plan, laboratory inspection and other test steps.

You may not qualify if:

(1) History of other tumors;
(2) Hematopoietic stem cell transplantation was performed within 6 weeks;
(3) Any target car-t treatment was performed within 3 months before the car-t treatment;
(4) Previous use of any commercially available PD-1 mAb;
(5) Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection;
(6) Active autoimmune diseases;
(7) Uncontrollable infection of active bacteria and fungi;
(8) HIV infection, syphilis infection; active hepatitis B or C: hepatitis B: HBV-DNA ≥ 1000IU / ml; hepatitis C: HCV RNA positive and liver function abnormal.
(9) Known central nervous system lymphoma.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Second Affiliated Hospital, School of Medicine, Zhejiang Universitylead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

Location

Related Publications (1)

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

Wenbin Qian, MD, PhD
2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
PRINCIPAL INVESTIGATOR

Study Design

Study Type: interventional
Phase: phase 1
Allocation: NA
Masking: NONE
Purpose: TREATMENT
Intervention Model: SEQUENTIAL
Sponsor Type: OTHER
Responsible Party: SPONSOR

Study Record Dates

First Submitted

May 6, 2020

First Posted

May 11, 2020

Study Start

June 18, 2020

Primary Completion

September 1, 2023

Study Completion

September 1, 2023

Last Updated

February 6, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing: Will not share

Locations

CN(1)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (4)

Study Arms (1)

CD19-7×19 CAR-T plus PD1 monoclonal antibody

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (1)

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Data Sharing

Locations