Evaluating BRL-201 for treating relapsed/refractory B-cell 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 study is testing a new CAR-T cell therapy called BRL-201 to see if it can help people with relapsed or hard-to-treat B-cell Non-Hodgkin Lymphoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Bioray Laboratories (Industry-sponsored)
• Drugs / interventions: CAR-T, immunotherapy
• Locations: 3 sites (Wuhan, Hubei and 2 other locations)
• Trial ID: NCT05741359 on ClinicalTrials.gov

What this trial studies

This clinical study is a multi-center, single-arm, open-label trial designed to assess the safety and efficacy of BRL-201, a CD19-targeted CAR-T cell therapy, in patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma. The study will enroll 12-18 subjects and utilize a '3 + 3' dose escalation design to determine the recommended phase 2 dose (RP2D). Participants will receive injections of CAR-T cells that are specifically engineered to target CD19, a protein commonly expressed on B-cell tumors. The study aims to evaluate the treatment's effectiveness based on measurable lesions as defined by established lymphoma response criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory aggressive B-cell Non-Hodgkin Lymphoma and measurable lesions.

Not a fit: Patients with central nervous system involvement or those who have not received adequate prior therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell Non-Hodgkin Lymphoma.

How similar studies have performed: Other studies utilizing CAR-T cell therapies for B-cell malignancies have shown promising results, indicating potential success for this approach.

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.

Where this trial is running

Wuhan, Hubei and 2 other locations

• Wuhan Union Hospital — Wuhan, Hubei, China (Recruiting)
• Tianjin Institute of Hematology — Tianjin, Tianjin Municipality, China (Recruiting)
• The First Affiliated Hospital of Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Wei Li, PhD

Conditions Non-hodgkin Lymphoma,B Cell