Acute Lymphoblastic Leukemia, Non Hodgkin Lymphoma
Conditions
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.
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.
Interventions
BIOLOGICALCD19-UCART
A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.
Sponsors
The First Affiliated Hospital of Zhengzhou University
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntary to participate in this clinical study and sign informed consent form; 2. The expected survival period is at least three months; 3. 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); 4. 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; 5. The test results show that CD19 is positive in the tumor; 6. 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 7. 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; 8. 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； 9. Heart function: good hemodynamic stability, and the left ventricular ejection fraction (LVEF) is higher than or equal to 55%; 10. Serum viruses such as HIV, TP, HBV(HBV-DNA) and HCV(HCV-DNA) are all negative; 11. ECOG activity status score: 0-2 points; 12. Accept the requirement that effective contraception be used throughout the study; 13. Willing to abide by the rules established in this study.
Exclusion criteria
1. Pregnant or lactating women; 2. Having a pregnancy plan in the next two years; 3. Has received graft-versus-host disease treatment in the past; 4. Has received allogeneic cell therapy in the past 6 weeks; 5. Has received allogeneic stem cell transplantation within the past 6 months; 6. Individual extramedullary relapse B-ALL; 7. Suffering from severe mental disorder; 8. Active autoimmune diseases requiring immunotherapy; 9. Has suffered from other malignant tumors in the past; 10. Patients with severe cardiovascular disease; 11. Prothrombin time or activated partial thromboplastin time or international normalized ratio \> \>1.5\*ULN； in the absence of anticoagulant therapy; 12. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) incidence | Day 0 up to 35 days after T cell infusion | Incidence of adverse events (AEs) defined as DLTs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Contacts
Primary ContactWei Li, M.D
Outcome results
None listed