Allogeneic CD19 CAR-T Cells for the Treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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CD19 CAR-T has been widely developed in patients with R/R ALL and has also been generally recognized by the industry. In 2017, the U.S. FDA approved Novartis's CD 19 CAR-T product Kymriah for the treatment of R/R ALL. 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 derived from healthy donors are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet reported a clinical study of 19 patients receiving allogeneic CAR-T cell ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, and the median sustained remission time was 4.1 moon. Allogeneic CAR-T cells are safe and effective for the treatment of ALL, and their clinical application range is expected to improve the remission rate and survival rate of patients with R/R ALL.

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 2018, New England Journal published the long-term follow-up data of CD19 CAR-T for relapse/refractory (R/R) ALL, 53 patients with r/r ALL who received a single infusion of CD19 CAR-T The response efficiency (CR+PR) reached 98%, of which about 83% of CR patients, with a median survival time of 12.9 months; greatly improved the remission rate and survival rate of r/r ALL patients. Nowadays,CD19 CAR-T has been widely developed in patients with R/R ALL and has also been generally recognized by the industry. In 2017, the U.S. FDA approved Novartis's CD CAR-T product Kymriah for the treatment of R/R ALL. 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 derived from healthy donors are not only sufficient in quantity and quality guaranteed, but also available at any time. In December 2020, lancet reported a clinical study of 19 patients receiving allogeneic CAR-T cell ALL. 14 patients were evaluated as CR/CRi (67%) 28 days after treatment, and the median sustained remission time was 4.1 moon. Allogeneic CAR-T cells are safe and effective for the treatment of ALL, and their clinical application range is expected to improve the remission rate and survival rate of patients with R/R ALL.

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

Conditions
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Relapse Leukemia, Refractory Leukemia

Intervention / Treatment
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* Biological: Allogeneic CD19 CAR-T cells


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 acute lymphoblastic leukemia (r/r B-ALL); The ECOG behavior status score is 0-2 points; Expected survival time ≥ 3 months; Flow cytometry confirms that the original 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. Exclusion Criteria: Primitive 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; 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>Subjects who meet the enrollment conditions will receive intravenous infusion of allogeneic CD19 CAR-T cells after pretreatment. | Biological: Allogeneic CD19 CAR-T cells<br>* infusion of allogeneic CD19 CAR-T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRR | Complete remission rate | From data of enrollment until the first documented progression of disease, up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival rate | From admission to the end of follow up, up to 2 years. |