CD19-CAR-T Cells in Patients With R/R B-ALL

Study Overview
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Brief Summary
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This is a single center, single arm, open-lable phase 1 study to determine the safety and efficacy of autologous or donor-derived allogeneic T cells expressing CD19 chimeric antigen receptors (referred to as CD19-CAR-T cells) in patients with relapsed or refractory acute B-cell lymphoblastic leukemia (R/R B-ALL).

Detailed Description
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Primary objective: To investigate the safety and efficacy of autologous or HLA-haploidentical Allo-CD19-CAR-T cells in the treatment of patients with relapsed or refractory acute B-cell lymphoblastic leukemia. Secondary objective: To Assess the patient's quality of life after receiving the treatment.

Official Title
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Phase I Study of the Safety and Efficacy of CD19-CAR-T Cells in Patients With Relapsed or Refractory Acute B-cell Lymphoblastic Leukemia (R/R B-ALL)

Conditions
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B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: CD19-CAR-T Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obtain Informed Consent Form (ICF) voluntarily signed by the patient; Age 3-70 years old; Primary resistant or relapsed B-cell line acute lymphoblastic leukemia; B cells are positive for CD19 expression; Peripheral blood tumor cell load <50%; 6. KPS score >50 points; 7. Normal liver and kidney function; 8. Normal heart function; 9. Good follow-up compliance; 10. Women of childbearing age (15-49 years old) must have a pregnancy test within 7 days before treatment and have a negative result; Men and women with fertility should agree to use effective contraception to ensure that during the study period and following 3 months after treatment the women will not get pregnant. Exclusion Criteria: Patients with non-B cell acute leukemia; Organ failure: Heart: Grade III and IV Liver: Class C with Child-Turcotte liver function classification Kidney: Renal failure and uremia Lung: severe respiratory failure Brain: Disabilities Active infection; Human immunodeficiency virus (HIV) positive; Acute and chronic graft-versus-host disease (GVHD)> Level 1； Pregnant or lactating women; Patients do not agree to use effective contraception during the treatment period and following 3 months; Patients who participated in other clinical studies at the same time; The researcher believes that there are other factors that are not suitable for inclusion in or influence the subject's participation in or completion of the study; Long-term use greater doses of hormones than physiological doses.

Ages Eligible for Study
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Minimum Age: 3 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: CD19-CAR-T Cells<br>Subjects will receive CD19-CAR-T Cells on Day 0 : 100% of total dose. | Biological: CD19-CAR-T Cells<br>* T cells purified from the PBMC of subjects or subjects' relatives which depends on their conditions, transduced with 4-1BB/CD3-ζ lentiviral vector, expanded in vitro for future administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate, ORR | The percentage of participants who achieved complete remission (CR) over all participants (CRR). The percentage of participants who achieved partial remission (PR) over all participants (PRR). | Up to Day90 after the CD19-CAR-T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of CAR-T cells remaining in vivo | Measure and analyze monthly | 2 years after cell infusion. | 
| The lifetime of CAR-T cells remaining in vivo | Measure and analyze monthly | 2 years after cell infusion. |