CD19-CAR-T in B-cell Malignancies Patients

Study Overview
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Brief Summary
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This is a single center, single arm, open-lable phase I study to determine the safety and efficacy of CD19-CAR-T cells in patients with refractory and relapsed B-cell malignancies.

Detailed Description
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This Phase I study is designed as a pilot trial evaluating the safety and of CD19-CAR-T cell therapy in subjects with refractory and relapsed B cell malignancies. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of CD19-CAR-T cells. Safety and efficacy of CD19-CAR-T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19-CAR-T cells therapy in patients with refractory and relapsed B-cell malignancies.

Official Title
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CD19-CAR-T for Patients With B Cell Malignancies

Conditions
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B-cell Malignancy

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: Relapsed and refractory CD19 positive B-cell acute malignancies with: Relapsed after competed remission, could not get competed remission after at more than 1 course of chemotherapy (including MRD≥0.1%); MRD≥0.1% after allogeneic hematopoietic stem cell transplantation(HSCT), or recurrence after complete remission or MRD ≥ 0.1% after HSCT; Refractory: at least two courses of chemotherapy did not achieve complete remission or MRD ≥ 0.1%; Patients must have evaluable evidence of disease, including minimal residual disease (MRD); Ph + patients who meet the following criteria can register:Failure to tolerate TKI or TKI treatment failure, or failure to transplant; Ages 1 to 70 years, including boundary values; ECOG score 0-3 points; Women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside. Exclusion Criteria: patients with organ failure: Heart: NYHA heart function grade IV; Liver: Grade C that achieves Child-Turcotte liver function grading; Kidney: kidney failure and uremia; Lung: symptoms of respiratory failure; Brain: a person with a disability; Active infections that are difficult to control; Human immunodeficiency virus (HIV) positive; Liver and kidney function: total bilirubin > 5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 5 × ULN, serum creatinine clearance rate 60mL / min; GVHD ≥ 2 or anti-GVHD treatment; Received allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion; Subject received anti-tumor treatment (chemotherapy, mAb, or hormone) for less than 1 week; Central nervous system white blood that is symptomatic or uncontrolled by systemic chemotherapy and intrathecal chemotherapy (a large number of tumor cells in CSF, white blood cell count >15WBCs/mL); intracranial hypertension or unconsciousness; respiratory failure; diffuse vascular internal coagulation; pregnant or lactating women; The patient does not agree to use effective contraception during the treatment period and for the next 3 months; Patients who participate in other clinical studies at the same time; The investigator believes that there are other factors that are not suitable for inclusion or influence the subject's participation or completion of the study.

Ages Eligible for Study
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Minimum Age: 1 Year
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>CD19-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest for 2 days before infusion. | Biological: CD19-CAR-T cells<br>* CD19-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest for 2 days before infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of adverse events | Percentage of participants with adverse events. | 6 months | 
| Objective remission rate(ORR) | The percentage of participants who achieved complete remission (CR) and partial remission over all participants. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-Free Survival(RFS ) |  | 6 months | 
| Overall-Survival(OS) |  | 6 months | 
| Persistence of CAR-T cells in vivo |  | 6 months |