Safety and Efficacy Evaluation of Next-generation CD19-UCART

Phase 1

Not yet recruiting

• Conditions: Non Hodgkin Lymphoma; Acute Lymphoblastic Leukemia
• Interventions: Biological: CD19-UCART

• Registration Number: NCT05381181
• Lead Sponsor: Bioray Laboratories

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.

Study Timeline

• Status Verified: 2022-05
• Study First Submitted: 2022-05-11
• Study First Submitted QC: 2022-05-15
• Study First Posted: 2022-05-19
• Last Update Submitted: 2023-01-25
• Last Update Posted: 2023-01-27
• Study Start: 2023-12-20
• Primary Completion: 2024-05-30
• Study Completion: 2026-05-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD19-UCART	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.