Safety and Efficacy Evaluation of Next-generation CD19-UCART

NCT ID: NCT05381181

Last Updated: 2023-01-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-20
• Study Completion Date: 2026-05-03

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.

Conditions

Acute Lymphoblastic Leukemia; Non Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CD19-UCART

Intervention Type: BIOLOGICAL

A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.

Interventions

CD19-UCART

A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

Bioray Laboratories

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yi Zhang, Prof.

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Zhengzhou University

Central Contacts

Wei Li, M.D

Role: CONTACT

wli@brlmed.com

+8602164340008

Other Identifiers

2021-BRL-301

Identifier Type: -

Identifier Source: org_study_id