Safety and Efficacy Evaluation of Next-generation CD19-UCART

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of Next-generation CD19-UCART in patients with relapsed or refractory B-cell hematological malignancies.

Detailed Description
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CD19-UCART is a kind of off-the-shelf product originated from health donor's PBMC. This is an open-label, single arm study to evaluate the safety and anti- tumor efficacy of Next-generation CD19-UCART in the treatment of relapsed or refractory B-cell hematological malignancies.

Official Title
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Clinical Study of the Safety and Efficacy of Next-generation Universal CD19 Chimeric Antigen Receptor T Cells in the Treatment of Relapsed or Refractory B Cell Malignancies

Conditions
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Acute Lymphoblastic Leukemia, Non Hodgkin Lymphoma

Intervention / Treatment
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* Biological: CD19-UCART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary to participate in this clinical study and sign informed consent form; The expected survival period is at least three months; There is no other severe cardiopulmonary disease, and the liver and kidney function are normal (except for the subject with tumor lesions in the liver and kidney); Patients cannot benefit from autologous CAR-T cell therapy due to T cell separation failure or CART amplification failure in the preparation of autologous CART, or the failure to complete apheresis or disease progression; Or the content of T cells in PBMC of peripheral blood is less than or equal to 10%; Or the disease is not effectively controlled within one month after autologous CAR-T transfusion, and the patient cannot receive CAR-T transfusion again; The test results show that CD19 is positive in the tumor; Patients with relapsed or refractory CD19-positive acute B-lymphocyte leukemia or B-cell non-Hodgkin's lymphoma. Patients with r/r B-ALL: 1 years old ≤ patient age ≤60 years. Patients with r/r B-NHL: 18 years old ≤ patient age ≤65 years old Hematological indicators meet the following conditions: 1) WBC count ≥ 1.5× 10^9/L; 2) Absolute value of neutrophils ≥ 0.8× 10^9/L; 3) Lymphocyte count ≥ 0.1× 10^9/L; 4) Hemoglobin ≥ 60 g/L; 5) Platelet count ≥ 20× 10^9/L; Blood biochemistry shall meet the following requirements 1) or 2): 1) patients with liver and kidney without tumor lesions: A) Total bilirubin (TBIL)≤1.5*ULN (upper limit of normal value), unless suffering from Gilbert's syndrome; B) aspartate aminotransferase (AST) ≤ 1.5 * ULN; C) ALT ≤ 1.5 * ULN; D) Scr ≤ 1.5 * ULN; E) Urea (URA) ≤ 1.5 * ULN; 2) patients with liver and kidney tumor lesions: a) TBIL≤5*ULN； b) AST≤5*ULN； c) ALT≤5*ULN； d) SCr≤5*ULN； e) Urea≤5*ULN； Heart function: good hemodynamic stability, and the left ventricular ejection fraction (LVEF) is higher than or equal to 55%; Serum viruses such as HIV, TP, HBV(HBV-DNA) and HCV(HCV-DNA) are all negative; ECOG activity status score: 0-2 points; Accept the requirement that effective contraception be used throughout the study; Willing to abide by the rules established in this study. Exclusion Criteria: Pregnant or lactating women; Having a pregnancy plan in the next two years; Has received graft-versus-host disease treatment in the past; Has received allogeneic cell therapy in the past 6 weeks; Has received allogeneic stem cell transplantation within the past 6 months; Individual extramedullary relapse B-ALL; Suffering from severe mental disorder; Active autoimmune diseases requiring immunotherapy; Has suffered from other malignant tumors in the past; Patients with severe cardiovascular disease; Prothrombin time or activated partial thromboplastin time or international normalized ratio > >1.5*ULN； in the absence of anticoagulant therapy; There is active infectious disease or need any major infection events of high-level antibiotics; 13. Any condition that, in the opinion of the investigator, may increase the subject's risk or interfere with the study results.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 65 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-UCART<br>All patients will be treated with at least 1 injection of CD19- UCART. A dose of 5x10^6/kg BW of CD19-UCART will be evaluated. If > 1/6 of DLT occurred, the dose would be reduced to 2.0x10^6/kg BW. | Biological: CD19-UCART<br>* A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) incidence | Incidence of adverse events (AEs) defined as DLTs | Day 0 up to 35 days after T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed. | At 12 weeks |