Clinical trial NCT06875063: GB5005 CART-cell Injection in the Treatment of Patients With CD19-positive RR B-NHL
Official title: The Safety, Tolerability, Efficacy, and Pharmacokinetic Characteristics of GB5005 Chimeric Antigen Receptor T-cell Injection in Treating Patients With CD19-positive Relapsed/Refractory B-cell Non-Hodgkin Lymphoma (B-NHL).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-hodgkin Lymphoma,B Cell
Relapsed Non-Hodgkin Lymphoma
Refractory Lymphoma
Chimeric Antigen Receptor T-cell
Lead sponsor: The First Affiliated Hospital of Xiamen University
Sponsor class: OTHER
First posted: 2025-03-13
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of GB5005 in patients with CD19-positive relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL).

Detailed description: Primary objectives: To evaluate the safety and tolerability of GB5005 in patients with CD19-positive relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL).

Secondary objectives: To assess the preliminary efficacy of GB5005 in patients with CD19-positive B-NHL; To describe the pharmacokinetic profile of GB5005 and observe its proliferation and persistence in the body; To explore the correlation between the pharmacokinetic characteristics of GB5005 and cytokine release syndrome (CRS) as well as neurological events.

Eligibility criteria: Inclusion Criteria:

1. The candidate is able to communicate effectively with researchers and sign informed consent forms in writing;
2. Age greater than or equal to 18 years old and less than or equal to 70 years old, regardless of gender; Sign informed consent form;
3. Non Hodgkin lymphoma confirmed by cytology and genetics;
4. Positive expression of CD19 in tumor cells confirmed by flow cytometry or pathological histology;
5. When screening, it meets the definition of recurrence or refractory: having received at least second-line or above systemic anti-tumor therapy (including autologous hematopoietic stem cell transplantation) containing rituximab (or other CD20 targeted drugs) and anthracycline drugs in the past, and disease progression (PD) or recurrence after the last treatment; Or recurrent patients who do not fully meet the above conditions but refuse chemotherapy and strongly demand CAR-T treatment;
6. There is no obvious evidence of central nervous system lymphoma on brain MRI;
7. Blood routine: Neutrophils ≥ 1.0 × 10 \^ 9/L; Hemoglobin ≥ 70 g/L; Platelets ≥ 50 × 10 \^ 9/L;
8. Coagulation function: fibrinogen ≥ 1.0 g/L; Activated partial thromboplastin time (APTT) ≤ ULN+10 s, prothrombin time (PT) ≤ ULN+3 s;
9. Liver and kidney function indicators: total bilirubin ≤ 1.5 times the upper limit of normal range (excluding Gilbert syndrome or hemolysis), ALT and AST ≤ 3.0 times the upper limit of normal range (ULN), serum creatinine ≤ 2.0 times the upper limit of normal range. If the above abnormalities are considered to be caused by tumor infiltration, they can be excluded;
10. Assessment of left ventricular ejection fraction (LVEF) ≥ 45% using echocardiography (ECHO) or radionuclide active vascular scanning (MUGA). (After corrective treatment and meeting the criteria, it can be included in the group);
11. Pulmonary function: Dyspnea ≤ CTCAE level 1 and SaO2 ≥ 92% in indoor air environment; 12. The physical fitness score of the Eastern Cooperative Oncology Group (ECOG) in the United States ranges from 0 to 2 points;
12. Expected survival is greater than 6 months; 14. The subjects have sufficient levels of functional organs during screening;
13. Female participants of childbearing age must undergo a serum pregnancy test during screening and before receiving pre-treatment chemotherapy, and the result must be negative. They are willing to use highly effective and reliable methods of contraception within one year after using the study treatment;
14. Male participants who engage in active sexual activity with women with reproductive potential must be willing to use highly effective and reliable methods of contraception within one year after using the study treatment. Moreover, all males are strictly prohibited from donating sperm within one year after receiving research treatment infusion during the study period.

Exclusion Criteria:

1. Patients with a history of allergies to serum albumin and DMSO in the past;
2. Active hepatitis B virus (HBV) (HBV-DNA positive), hepatitis C virus antibody (HCV) (HCV-RNA positive), or human immunodeficiency virus (HIV) infection;
3. Within the past 2 years, terminal organ damage caused by autoimmune diseases such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, or the need for systemic use of immunosuppressive or other systemic disease control drugs;
4. History of unstable angina, myocardial infarction, coronary angioplasty, or significant heart disease within one year of enrollment;
5. Primary central nervous system tumors or hematological tumors with central nervous system metastases;
6. Uncontrolled mental illness;
7. Merge other life-threatening severe organ failure;
8. Participated in other clinical studies within 4 weeks;
9. Received live vaccination within 4 weeks of enrollment;
10. Using prohibited drugs: a. Hormones: Corticosteroids (defined as\>20mg/day prednisone or equivalent) used at therapeutic doses within 7 days prior to leukocyte collection. But the use of physiological substitutes, local and inhaled steroids is allowed. b. Chemotherapy: rescue chemotherapy, including tyrosine kinase inhibitors (TKIs), received within 1 week before leukocyte collection. c. Donor lymphocyte infusion (DLI) received within 4 weeks before leukocyte collection. d. graft-versus-host disease (GvHD) treatment: systemic anti GVHD treatment received within 3 months before GB5005 cell infusion. e. Alenumab used within 6 months before leukocyte collection, or chlorofarabin or cladribin used within 3 months. f. Checkpoint inhibitors or stimulants used before enrollment (excluding those with more than 3 biological half lives);
11. Patients with known history of lung injury or hemorrhagic cystitis associated with cyclophosphamide treatment;
12. Women who are already pregnant, preparing for pregnancy during the trial period, or breastfeeding;

13：As per the investigator's judgment, the subject is unlikely to complete all required visits or procedures stipulated in the protocol (including the follow-up period) or has insufficient compliance with the study.

Primary outcomes:
measure: Complete remission (CR)
timeFrame: Up to 3 months
Secondary outcomes:
measure: Recurrence free survival time (RFS)
timeFrame: Up to 24 months
measure: Overall survival（OS）
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Xiamen
country: China
facility: Bing Xu
state: Fujian
Study officials:
affiliation: The First Aiffiliated hosptical of xiamen University
name: Bing Xu
role: PRINCIPAL_INVESTIGATOR
References: