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

NCT ID: NCT05741359

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-25
• Study Completion Date: 2027-01-15

Brief Summary

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

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.

Conditions

Non-hodgkin Lymphoma,B Cell

Study Design

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

Study Groups

Treatment group

5- 10.0×10\^6/kgBW

Group Type: EXPERIMENTAL

CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection

Intervention Type: DRUG

CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection

Interventions

CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection

CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection

Intervention Type: DRUG

Other Intervention Names

BRL-201

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Bioray Laboratories

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Li

Role: STUDY_CHAIR

Bioray Laboratories

Locations

Wuhan Union Hospital

Wuhan, Hubei, China

Site Status: RECRUITING

Tianjin Institute of Hematology

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei Li, PhD

Role: CONTACT

wli@brlmed.com

18621670308

Facility Contacts

Heng Mei, PhD

Role: primary

Rugui qiu, PhD

Role: primary

He Huang, PhD

Role: primary

Other Identifiers

2022-BRL-201

Identifier Type: -

Identifier Source: org_study_id