Trial Title:
Zanubrutinib in Maintenance Therapy of DLBCL Patients With Initial Remission
NCT ID:
NCT05596097
Condition:
Diffuse Large B-cell Lymphoma (DLBCL)
Conditions: Official terms:
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Zanubrutinib
Conditions: Keywords:
Diffuse Large B-cell Lymphoma (DLBCL)
Maintenance Therapy
Zanubrutinib
Rituximab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
According to the initial treatment plan of the patients, the patients were divided into
R-CHOP and R-chemo groups. Both groups received zanubrutinib maintenance therapy after
induction and consolidation therapy reached the maximum curative effect. With event-free
survival (EFS) as the primary endpoint, partial remission (PR) to CR conversion rate,
progression-free survival (PFS), and overall survival (OS) as secondary endpoints,
adverse events (AEs) were assessed. ) incidence and related mechanisms during the study
period.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zanubrutinib
Description:
Zanubrutinib, 180mg, bid, p.o., d1-28; Treatment cycles every 28 days
Arm group label:
experimental group
Summary:
This trial is a single-center, single-arm, prospective clinical study to investigate the
efficacy and safety of zanubrutinib maintenance therapy in patients with diffuse large
B-cell lymphoma (DLBCL) in Initial remission. The patients were divided into two
categories: 1) Zanubrutinib maintenance therapy was started after R-CHOP induction and
consolidation therapy reached maximum efficacy; 2) Initiate zanubrutinib maintenance
therapy after maximal response to induction and consolidation therapy with or without
rituximab (R-chemo). Therefore, the data in this study will reflect the efficacy and
safety of zanubrutinib in the maintenance treatment of DLBCL patients with initial
remission, and will provide new insights into the clinical application of zanubrutinib.
Detailed description:
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive malignant lymphoma,
and because it is sensitive to chemotherapy, approximately 50% to 70% of patients can
achieve a cure after first-line treatment. However, in recent years, it has been found
that more than 30% of patients experience relapse within two years after first-line
treatment, which is a serious health threat and requires urgent secondary treatment. To
reduce the recurrence of DLBCL and improve the survival rate of patients, clinical
researchers have long been dedicated to the maintenance treatment of DLBCL patients after
first-line treatment, aiming to kill tumor cells and reduce the risk of recurrence
through continuous drug administration, thus enabling patients to survive with the tumor
for a long time. Several clinical trials are currently underway with rituximab,
ibrutinib, lenalidomide, and thalidomide, but safer and more effective maintenance
regimens have yet to be identified.
Zanubrutinib, a new-generation BTK inhibitor, is the first anti-tumor drug developed
locally in China and approved for marketing in the US. Zanubrutinib inhibits the
activation of the BCR signaling pathway by specifically binding to cysteine residues at
the active site of BTK to form a covalent bond that irreversibly inactivates them,
thereby inhibiting BTK and improving the tumor microenvironment, inhibiting malignant
proliferation and inducing apoptosis in tumor B cells. Several clinical studies have
demonstrated that ibrutinib alone and in combination is no less effective than ibrutinib
in the treatment of DLBCL, and has a better safety and tolerability profile.
This study proposes to use Zanubrutinib for maintenance treatment in DLBCL patients in
remission after primary treatment and to evaluate the efficacy and safety of patients to
provide new insights into the clinical use of Zanubrutinib.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with DLBCL who are diagnosed according to the 2021 NCCN Guidelines for
B-cell Lymphoma, aged ≥18 years;
2. Don't received treatment;
3. Measurable lesions: at least 1 lymph node lesion > 1.5 cm in longest dimension, or
at least 1 extranodal lesion > 1.0 cm in longest dimension, and at least 2
measurable lesions accurately measured vertical diameter;
4. Clinical stage II (not suitable for local radiotherapy), III, IV (Ann Arbor stage);
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
5. Intermediate-high-risk /high-risk group: International Prognostic Index (IPI) score
3-5, aa-IPI score 2-3 or NCCN-IPI score ≥4;
6. Expression of MYC, BCL-2 and BCL-6 (detected by immunohistochemistry, qualitative or
quantitative detection), or MYD88, CD79A/CD79B [9] and TP53 genetic abnormality
[10];
7. Patients with non-bone marrow invasion:
1. The absolute value of neutrophils≥1.5×109/L
2. Platelets ≥100×109/L (judged by the investigator according to the condition,
the minimum can be ≥75×109/L)
3. Hemoglobin ≥ 90g/L;
9. The level of biochemical indicators meets the following requirements:
1. Renal function: endogenous creatinine clearance rate > 30ml/min;
2. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤ 3 × upper limit of normal range (ULN); total bilirubin ≤ 2 × ULN (unless Gilbert
syndrome is diagnosed);
3. Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated
partial thromboplastin time (aPTT) ≤ 1.5×ULN; 9. life expectancy ≥ 3 months; 10. The
patient and family members agree and sign an informed consent form.
Exclusion Criteria:
1. Lymphoma with central nervous system invasion or mediastinal large B-cell lymphoma,
diagnosis or treatment of malignant tumors other than DLBCL;
2. Cannot tolerate zanubrutinib treatment, or have hypersensitivity reactions to any
components of the study drug;
3. Significant cardiovascular disease, including:
1. Myocardial infarction within 6 months prior to screening;
2. Unstable angina pectoris occurring within 3 months prior to screening;
3. Clinically significant arrhythmias (eg, sustained ventricular tachycardia,
ventricular fibrillation, torsades de pointes);
4. QTc (corrected by Fridericia formula): >450ms in men, >470ms in women, or other
ECG abnormalities, including history of second-degree type II atrioventricular
(AV) block or third-degree AV block;
5. Any grade 3 or 4 heart disease as defined by the New York Heart Association
(NYHA) functional class;
6. Echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) ≤40%
(AHA, 2022);
7. Uncontrolled hypertension at screening, manifested as systolic blood pressure
≥180 mmHg and diastolic blood pressure ≥110 mmHg on at least two consecutive
blood pressure measurements;
4. Requires continuous treatment with strong or moderate CYP3A inhibitors/inducers.
Patients are not eligible if they have taken strong or moderate CYP3A
inhibitors/inducers within 7 days prior to the first dose of study drug (or have
taken these drugs for less than 5 half-lives);
5. Hepatitis B virus (HBV-DNA) ≥ 1x10^3 copies/mL or HBV-DNA > 200 IU/mL or active
hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Serologically
positive;
6. Obvious bleeding tendency, such as a history of stroke, intracranial hemorrhage
within 6 months, or a history of surgery within 4 weeks;
7. Serious infectious diseases at the same time;
8. Refuse to take reliable contraceptive methods during pregnancy, lactation or
appropriate age;
9. Participate in another clinical trial of lymphoma treatment at the same time;
10. Unsuitable for enrollment by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Hospital of Lanzhou University
Address:
City:
Lanzhou
Zip:
730000
Country:
China
Contact:
Last name:
Bei Liu, MD
Phone:
+8613809319379
Email:
liubeiff@163.com
Start date:
October 30, 2022
Completion date:
July 30, 2026
Lead sponsor:
Agency:
LanZhou University
Agency class:
Other
Collaborator:
Agency:
Beigene (Beijing) Biotechnology Co., Ltd
Agency class:
Other
Source:
LanZhou University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05596097
