Clincosm LogoSign in Get a demo

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

Sponsor
Bioray Laboratories (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05741359
Collaborator
Institute of Hematology ＆ Blood Diseases Hospital，Chinese Academy of Medical Sciences (Other), Zhejiang University (Other), Wuhan Union Hospital, China (Other)
18
Enrollment
3
Arms
11.5
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: CD19-targeted non-viral PD1 site-specific integrated CAR-T cell injection
 Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
Total target count of CD3+CAR+ viable cellsTotal target count of CD3+CAR+ viable cells
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Anticipated Study Start Date :
Mar 30, 2023
Anticipated Primary Completion Date :
Jan 20, 2024
Anticipated Study Completion Date :
Mar 15, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: BRL-201 A

Total target count of CD3+CAR+ viable cells

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

    		•
    Experimental: BRL-201 B

    Total target count of CD3+CAR+ viable cells

    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

    		•
    Experimental: BRL-201 C

    Total target count of CD3+CAR+ viable cells

    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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. DLT [Within 28 Days After BRL-201 Infusion]

      The number and severity of dose-limiting toxicity (DLT) events

    2. AEs [Up to 24 Months After BRL-201 Infusion]

      The total number, incidence, and severity of AEs

    3. RP2D [Within 28 Days After BRL-201 Infusion]

      The recommended phase 2 dose

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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;

    1. 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;

    2. 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;

    3. Conditions (e.g., intestinal obstruction or vascular compression) requiring emergency treatment due to tumor masses;

    4. History of severe immediate hypersensitivity to any drug to be used in this study;

    5. Vaccination of live vaccines, excluding corona virus disease 2019 (COVID-19) vaccines, within ≤ 6 weeks before the start of the pretreatment regimen;

    6. Any circumstances that possibly increase the risk of subjects or interfere with the study results as judged by the investigator.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Bioray Laboratories
    • Institute of Hematology ＆ Blood Diseases Hospital，Chinese Academy of Medical Sciences
    • Zhejiang University
    • Wuhan Union Hospital, China

    Investigators

    • Study Chair: Wei Li, Bioray Laboratories

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bioray Laboratories
    ClinicalTrials.gov Identifier:
    NCT05741359
    Other Study ID Numbers:
    • 2022-BRL-201
    First Posted:
    Feb 23, 2023
    Last Update Posted:
    Feb 23, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell

    Study Results

    No Results Posted as of Feb 23, 2023