Safety and Efficacy Evaluation of Next-generation CD19-UCART

NCT05381181 | Not Yet Recruiting Phase 1

• 1 other identifier: 2021-BRL-301
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Lymphoblastic Leukemia; Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLTs) incidence

  Incidence of adverse events (AEs) defined as DLTs

  Day 0 up to 35 days after T cell infusion

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  At 12 weeks

Other Outcomes (3)

• Duration of response (DOR)

  up to 2 years after T cell infusion

• Progress free survival (PFS)

  up to 2 years after T cell infusion

• Overall survival (OS)

  up to 2 years after T cell infusion

Study Arms (1)

CD19-UCART

EXPERIMENTAL

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.

Biological: CD19-UCART

Interventions

CD19-UCART BIOLOGICAL

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

CD19-UCART

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary to participate in this clinical study and sign informed consent form;
• The expected survival period is at least three months;
• 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);
• 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;
• The test results show that CD19 is positive in the tumor;
• 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
• 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;
• 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；
• Heart function: good hemodynamic stability, and the left ventricular ejection fraction (LVEF) is higher than or equal to 55%;
• Serum viruses such as HIV, TP, HBV(HBV-DNA) and HCV(HCV-DNA) are all negative;
• ECOG activity status score: 0-2 points;
• Accept the requirement that effective contraception be used throughout the study;
• Willing to abide by the rules established in this study.

You may not qualify if:

• Pregnant or lactating women;
• Having a pregnancy plan in the next two years;
• Has received graft-versus-host disease treatment in the past;
• Has received allogeneic cell therapy in the past 6 weeks;
• Has received allogeneic stem cell transplantation within the past 6 months;
• Individual extramedullary relapse B-ALL;
• Suffering from severe mental disorder;
• Active autoimmune diseases requiring immunotherapy;
• Has suffered from other malignant tumors in the past;
• Patients with severe cardiovascular disease;
• Prothrombin time or activated partial thromboplastin time or international normalized ratio \> \>1.5\*ULN； in the absence of anticoagulant therapy;
• 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.

Sponsors & Collaborators

• Bioray Laboratories: lead
• The First Affiliated Hospital of Zhengzhou University: collaborator

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Study Officials

• Yi Zhang, Prof.

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Li, M.D

CONTACT

+8602164340008; wli@brlmed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 19, 2022
• Study Start: December 20, 2023
• Primary Completion: May 30, 2024
• Study Completion: May 3, 2026
• Last Updated: January 27, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share