Safety and Efficacy Evaluation of Next-generation CD19-UCART

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05381181
• Other study ID #: 2021-BRL-301
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: December 20, 2023
• Est. completion date: May 3, 2026

Study information

• Verified date: May 2022
• Source: Bioray Laboratories
• Contact: Wei Li, M.D
• Phone: +8602164340008
• Email: wli[@]brlmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: May 3, 2026
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Non Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bioray Laboratories	The First Affiliated Hospital of Zhengzhou University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of response (DOR)	DOR is defined as the time from the first objective response to disease progression or death due to disease relapse or drug-related toxicity	up to 2 years after T cell infusion
Other	Progress free survival (PFS)	PFS is defined as the time from the T cell infusion date to the date of disease progression or death from any cause	up to 2 years after T cell infusion
Other	Overall survival (OS)	OS is defined as the time from the date of leukapheresis until death from any cause	up to 2 years after T cell infusion
Primary	Dose Limiting Toxicities (DLTs) incidence	Incidence of adverse events (AEs) defined as DLTs	Day 0 up to 35 days after T cell infusion
Secondary	Objective Response Rate (ORR)	Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed.	At 12 weeks