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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Non-hodgkin Lymphoma,B Cell

Intervention / Treatment
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* Biological: Allogeneic CD19 CR-T cell


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Allogeneic CD19 CR-T cell infusion | Biological: Allogeneic CD19 CR-T cell<br>* Allogeneic CD19 CR-T cell infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of patients in complete remission in total treated patients | From date of initial treatment to the end of follow up, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival rate | Time from initiation of trial treatment to death | From admission to the end of follow up, up to 2 years |