Clinical trial NCT05381181: Safety and Efficacy Evaluation of Next-generation CD19-UCART
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Non Hodgkin Lymphoma
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
First posted: 2022-05-19
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs) incidence
timeFrame: Day 0 up to 35 days after T cell infusion
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: At 12 weeks
Other outcomes:
measure: Duration of response (DOR)
timeFrame: up to 2 years after T cell infusion
measure: Progress free survival (PFS)
timeFrame: up to 2 years after T cell infusion
measure: Overall survival (OS)
timeFrame: up to 2 years after T cell infusion
Locations:
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Yi Zhang, Prof.
role: PRINCIPAL_INVESTIGATOR
References: