Safety and Efficacy Evaluation of Next-generation CD19-UCART
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CD19-UCART 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
A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.
|
Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicities (DLTs) incidence [Day 0 up to 35 days after T cell infusion]
Incidence of adverse events (AEs) defined as DLTs
Secondary Outcome Measures
- Objective Response Rate (ORR) [At 12 weeks]
Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed.
Other Outcome Measures
- Duration of response (DOR) [up to 2 years after T cell infusion]
DOR is defined as the time from the first objective response to disease progression or death due to disease relapse or drug-related toxicity
- Progress free survival (PFS) [up to 2 years after T cell infusion]
PFS is defined as the time from the T cell infusion date to the date of disease progression or death from any cause
- Overall survival (OS) [up to 2 years after T cell infusion]
OS is defined as the time from the date of leukapheresis until death from any cause
Eligibility Criteria
Criteria
Inclusion Criteria:
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Voluntary to participate in this clinical study and sign informed consent form;
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The expected survival period is at least three months;
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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);
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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;
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The test results show that CD19 is positive in the tumor;
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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
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Hematological indicators meet the following conditions: 1) WBC count ≥ 1.5× 109/L; 2) Absolute value of neutrophils ≥ 0.8× 109/L; 3) Lymphocyte count ≥ 0.1× 109/L; 4) Hemoglobin ≥ 60 g/L; 5) Platelet count ≥ 20× 109/L;
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Blood biochemistry shall meet the following requirements 1) or 2): 1) patients with liver and kidney without tumor lesions: A) Total bilirubin (TBIL)≤1.5ULN (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≤5ULN； b) AST≤5ULN； c) ALT≤5ULN； d) SCr≤5ULN； e) Urea≤5ULN；
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Heart function: good hemodynamic stability, and the left ventricular ejection fraction (LVEF) is higher than or equal to 55%;
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Serum viruses such as HIV, TP, HBV(HBV-DNA) and HCV(HCV-DNA) are all negative;
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ECOG activity status score: 0-2 points;
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Accept the requirement that effective contraception be used throughout the study;
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Willing to abide by the rules established in this study.
Exclusion Criteria:
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Pregnant or lactating women;
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Having a pregnancy plan in the next two years;
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Has received graft-versus-host disease treatment in the past;
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Has received allogeneic cell therapy in the past 6 weeks;
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Has received allogeneic stem cell transplantation within the past 6 months;
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Individual extramedullary relapse B-ALL;
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Suffering from severe mental disorder;
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Active autoimmune diseases requiring immunotherapy;
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Has suffered from other malignant tumors in the past;
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Patients with severe cardiovascular disease;
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Prothrombin time or activated partial thromboplastin time or international normalized ratio > >1.5*ULN； in the absence of anticoagulant therapy;
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Bioray Laboratories
- The First Affiliated Hospital of Zhengzhou University
Investigators
- Principal Investigator: Yi Zhang, Prof., The First Affiliated Hospital of Zhengzhou University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-BRL-301