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Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma (CAR-T)

Primary Purpose

Non-hodgkin Lymphoma,B Cell

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Allogeneic CD19 CR-T cell

About this trial

This is an interventional treatment trial for Non-hodgkin Lymphoma,B Cell

Eligibility Criteria

14 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

14-70 years old (including 14, 70 years old), no gender limit;
According to the 2020 World Health Organization (WHO) diagnostic criteria, it is diagnosed as relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL);
The ECOG behavior status score is 0-2 points;
Expected survival time ≥ 3 months;
Tumor cells express CD19;
Those who have failed autologous CAR-T cell preparation or autologous CAR-T cell therapy under the existing technical conditions;
No serious heart, lung, liver, or kidney disease;
Ability to understand and willing to sign the informed consent form for this trial.

Cell donors must meet the following criteria to participate in this study:

18-60 years old, no gender limit;
A fully matched/half-matched donor with the patient's HLA match;

9) No contraindications to peripheral blood apheresis

Exclusion Criteria:

Tumor cells do not express CD19;
Active infection;
Abnormal liver function (total bilirubin>1.5×ULN, ALT>2.5×ULN), abnormal renal function (serum creatinine>1.5×ULN);
People with unstable angina or New York Heart Association class 3/4 congestive heart failure, multiple organ dysfunction;
HIV/AIDS patients;
Those who need long-term anticoagulation (warfarin or heparin), antiplatelet (aspirin, dose>300mg/d; clopidogrel, dose>75mg/d) treatment;
Those who received radiotherapy within 4 weeks before the start of the study (blood sampling);
Known or suspected drug abuse or alcohol dependence;
People with mental illness or other conditions cannot obtain informed consent, and cannot cooperate with the requirements of completing the experimental treatment and inspection procedures;
Participated in other clinical trials within 30 days;
Pregnant or lactating women, male subjects (or their partners) or female subjects have a pregnancy plan during the study period to 6 months after the end of the test, and are unwilling to use a medically approved effective contraceptive measure during the test period (Such as intrauterine contraceptive devices or condoms);
Those who are judged by the investigator to be unsuitable to participate in this trial

Sites / Locations

Li YuRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment group

Arm Description

Allogeneic CD19 CR-T cell infusion

Outcomes

Primary Outcome Measures

Overall response rate

Percentage of patients in complete remission in total treated patients

Secondary Outcome Measures

overall survival rate

Time from initiation of trial treatment to death

Full Information

NCT ID

NCT05143112

First Posted

November 22, 2021

Last Updated

November 22, 2021

Sponsor

Shenzhen University General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05143112

Brief Title

Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma

Acronym

CAR-T

Official Title

Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Recruiting

Study Start Date

February 5, 2021 (Actual)

Primary Completion Date

February 2024 (Anticipated)

Study Completion Date

February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shenzhen University General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Preclinical and clinical studies of CD19 CAR-T in r/r B-NHL have been extensively carried out. At the beginning of 2020, MorphoSys submitted its company-targeted CD19 monoclonal antibody to the FDA for r/r DLBL treatment and obtained FDA priority approval. It further confirms the safety and effectiveness of CD19 as a therapeutic target in r/r B-NHL. However, these CAR-T cells are constructed from patients' autologous T cells, and the production and preparation time is long; on the other hand, most patients have received multiple chemotherapy before CAR-T treatment, and the quantity and quality of T cells often cannot meet the needs of clinical treatment. It is also an important factor leading to the failure of CAR-T cell therapy, which limits the large-scale clinical application of CAR-T. T cells sourced from healthy people are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet[2] reported a clinical study of 19 patients receiving allogeneic CAR-T cell therapy for B-ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, with a median sustained remission Time 4.1 months. Allogeneic CAR-T cells are safe and effective for the treatment of B-cell malignant diseases, and their clinical application range is expected to further improve the remission rate and survival rate of patients with R/R B-cell non-Hodgkin's lymphoma.

Detailed Description

Chimeric antigen receptor (CAR) T cells enable T cells to recognize and kill tumor cells that express specific antigens through genetic engineering. CD19 is expressed on the membrane surface of pre-B cells and mature B cells, but not on the surface of T cells and normal granulocytes. It is an ideal therapeutic target for B cell-derived tumors. A large number of previous studies have confirmed that CD19 CAR-T cells are a safe and effective method for the treatment of ALL. In 2019, Locke FL[1] et al. reported a clinical study of CD19 CAR-T for r/r DLBL. 119 patients were enrolled. The objective response rate was 83%, the CR rate was 58%, and the median progression-free survival was 5.9. Months. Greatly improved the patient's prognosis. Preclinical and clinical studies of CD19 CAR-T in r/r B-NHL have been extensively carried out. At the beginning of 2020, MorphoSys submitted its company-targeted CD19 monoclonal antibody to the FDA for r/r DLBL treatment and obtained FDA priority approval. It further confirms the safety and effectiveness of CD19 as a therapeutic target in r/r B-NHL. However, these CAR-T cells are constructed from patients' autologous T cells, and the production and preparation time is long; on the other hand, most patients have received multiple chemotherapy before CAR-T treatment, and the quantity and quality of T cells often cannot meet the needs of clinical treatment. It is also an important factor leading to the failure of CAR-T cell therapy, which limits the large-scale clinical application of CAR-T. T cells sourced from healthy people are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet[2] reported a clinical study of 19 patients receiving allogeneic CAR-T cell therapy for B-ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, with a median sustained remission Time 4.1 months. Allogeneic CAR-T cells are safe and effective for the treatment of B-cell malignant diseases, and their clinical application range is expected to further improve the remission rate and survival rate of patients with R/R B-cell non-Hodgkin's lymphoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-hodgkin Lymphoma,B Cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Experimental

Arm Description

Allogeneic CD19 CR-T cell infusion

Intervention Type

Biological

Intervention Name(s)

Allogeneic CD19 CR-T cell

Intervention Description

Allogeneic CD19 CR-T cell infusion

Primary Outcome Measure Information:

Title

Overall response rate

Description

Percentage of patients in complete remission in total treated patients

Time Frame

From date of initial treatment to the end of follow up, up to 2 years

Secondary Outcome Measure Information:

Title

overall survival rate

Description

Time from initiation of trial treatment to death

Time Frame

From admission to the end of follow up, up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 14-70 years old (including 14, 70 years old), no gender limit; According to the 2020 World Health Organization (WHO) diagnostic criteria, it is diagnosed as relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL); The ECOG behavior status score is 0-2 points; Expected survival time ≥ 3 months; Tumor cells express CD19; Those who have failed autologous CAR-T cell preparation or autologous CAR-T cell therapy under the existing technical conditions; No serious heart, lung, liver, or kidney disease; Ability to understand and willing to sign the informed consent form for this trial. Cell donors must meet the following criteria to participate in this study: 18-60 years old, no gender limit; A fully matched/half-matched donor with the patient's HLA match; 9) No contraindications to peripheral blood apheresis Exclusion Criteria: Tumor cells do not express CD19; Active infection; Abnormal liver function (total bilirubin>1.5×ULN, ALT>2.5×ULN), abnormal renal function (serum creatinine>1.5×ULN); People with unstable angina or New York Heart Association class 3/4 congestive heart failure, multiple organ dysfunction; HIV/AIDS patients; Those who need long-term anticoagulation (warfarin or heparin), antiplatelet (aspirin, dose>300mg/d; clopidogrel, dose>75mg/d) treatment; Those who received radiotherapy within 4 weeks before the start of the study (blood sampling); Known or suspected drug abuse or alcohol dependence; People with mental illness or other conditions cannot obtain informed consent, and cannot cooperate with the requirements of completing the experimental treatment and inspection procedures; Participated in other clinical trials within 30 days; Pregnant or lactating women, male subjects (or their partners) or female subjects have a pregnancy plan during the study period to 6 months after the end of the test, and are unwilling to use a medically approved effective contraceptive measure during the test period (Such as intrauterine contraceptive devices or condoms); Those who are judged by the investigator to be unsuitable to participate in this trial

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Li Yu, Dr

Phone

+8675521839178

liyu@vip.163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Li Yu, Dr

Organizational Affiliation

Shenzhen University General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Li Yu

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Li Yu

Phone

+8675521839178

changhuayu@126.com

12. IPD Sharing Statement

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Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Lymphoma

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