The Safety and Efficacy of BRL-201 in the Treatment of r/r B Lymphocyte Non-Hodgkin Lymphoma

A Phase I/II Clinical Study of the Safety and Efficacy of CD19-targeted Non-viral PD1 Site-specific Integrated CAR-T Cell Injection (BRL-201) in the Treatment of Relapsed or Refractory B Lymphocyte Non-Hodgkin Lymphoma

This is a multi-center, single-arm, open-label clinical study, and the sample size is set to 12-18 subjects.

Study Overview

• Status: Recruiting
• Conditions: Non-hodgkin Lymphoma,B Cell
• Intervention / Treatment: Drug: CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection

Detailed Description

This is a multi-center, single-arm, open-label clinical study, and the sample size is set to 12-18 subjects. Based on the "3 + 3" dose escalation design principle, subjects will be divided into 3 groups from low dose to high dose in sequence (Group A; Group B; Group C. Additional subjects will be enrolled into the RP2D group to ensure that 6-9 efficacy-evaluable subjects are available in the RP2D group before entering the phase II study.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei Li, PhD; Phone Number: 18621670308; Email: wli@brlmed.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Wuhan Union Hospital
      • Contact: Heng Mei, PhD
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Recruiting
      • Tianjin Institute of Hematology
      • Contact: Rugui qiu, PhD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
      • Contact: He Huang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing to participate in this clinical study and sign an informed consent form;
2. Age ≥ 18 years old;
3. Estimated survival time ≥ 3 months;
4. Presence of at least one measurable lesion as assessed according to Lugano Classification 2014 for response assessment in lymphomas (i.e., the cross-sectional images obtained by CT show that the long diameter of lymph node lesions is > 15 mm or the long diameter of extranodal lesions is > 10 mm, and FDG-PET scan results are positive). Lesions, for which radiotherapy was provided, can be regarded as measurable lesions only if there is an unequivocal progression after radiotherapy;
5. Histopathologically confirmed aggressive B-NHL; positive expression of CD19 in tumors detected by immunohistochemistry or flow cytometry; pathological types of B-NHL (according to WHO Lymphoma Classification 2016);
6. Relapsed or refractory diseases;
7. Subjects who must receive adequate prior therapy;
8. Absence of invasion of central nervous system (CNS) lymphoma by cranial magnetic resonance imaging (MRI);
9. Hematological parameters meeting the requirements;
10. Blood biochemistry meeting the requirements;
11. LVEF ≥ 55%;
12. No severe pulmonary disorders;
13. Toxic reactions induced by prior anti-lymphoma therapy must be stable and resolved to grade ≤ 1;
14. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
15. Patients with physical conditions for apheresis of peripheral blood; 16 . Willing to abide by the rules formulated in the study protocol.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Subjects who previously received allogeneic cell therapies, including allogeneic stem cell transplant;
3. Subjects who previously received anti-CD19 targeted therapy, except those who receive BRL-201 and are eligible to receive reinfusion in this study;
4. Prior treatment with any CAR-T cell product or other genetically modified T cell therapies;
5. History of Richter's transformation of chronic lymphocytic leukemia (CLL);
6. Presence of uncontrollable fungal, bacterial, viral, or other infections requiring systemic therapy. Patients can be enrolled if the simple urinary tract infection or pharyngitis responds to treatment;
7. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA titer higher than the upper limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis test positive;
8. Severe mental disorders; history of CNS disorders (e.g., epileptic seizure, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any CNS-involved autoimmune disorders);
9. Active autoimmune disorders requiring immunotherapy, including but not limited to end organ damages caused by autoimmune disorders (e.g., Crohn's disease, rheumatoid arthritis, and systemic lupus erythematosus) in the past 2 years, or requiring systemic application of immunosuppressive drugs or other drugs for systemic control of diseases;
10. Primary immunodeficiency;
11. History of other malignancies;
12. Patients with severe cardiovascular disorders, including but not limited to those with lymphoma infiltration in the cardiac atrium or ventricles and those with a history of myocardial infarction, cardioangioplasty or stent implantation, unstable angina, or other clinically significant heart diseases within 12 months before enrollment;
13. History of deep venous thrombosis or pulmonary embolism within 6 months before enrollment;
14. Patients who are receiving oral anticoagulant therapy; prothrombin time (PT), activated partial thromboplastin time (APTT), or international normalized ratio (INR) > 1.5 × ULN without anticoagulant therapy;
15. Presence of any indwelling tube or catheter (e.g., tube or catheter for percutaneous nephrostomy, indwelling catheter, or catheter in pleural cavity/peritoneal cavity/pericardium). Dedicated central venous access catheters (e.g., Port-a-Cath or Hickman catheter) are permitted;
16. Lymphoma cells detected in cerebrospinal fluid, presence of brain metastases, history of CNS lymphoma, or history of lymphoma cells detected in cerebrospinal fluid or brain metastases;
17. Conditions (e.g., intestinal obstruction or vascular compression) requiring emergency treatment due to tumor masses;
18. History of severe immediate hypersensitivity to any drug to be used in this study;
19. Vaccination of live vaccines, excluding corona virus disease 2019 (COVID-19) vaccines, within ≤ 6 weeks before the start of the pretreatment regimen;
20. Any circumstances that possibly increase the risk of subjects or interfere with the study results as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; 5- 10.0×10^6/kgBW	Drug: CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection; CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection; Other Names: BRL-201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	The number and severity of dose-limiting toxicity (DLT) events	Within 28 Days After BRL-201 Infusion
AEs	The total number, incidence, and severity of AEs	Up to 24 Months After BRL-201 Infusion
RP2D	The recommended phase 2 dose	Within 28 Days After BRL-201 Infusion

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: Zhejiang University; Chinese Academy of Medical Sciences; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Investigators: Study Chair: Wei Li, Bioray Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: 2022-BRL-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No