Trial Title:
Orelabrutinib Combined With R-CDOP for DLBCL Patients With High-risk of CNS Relapse Defined by CNS-IPI
NCT ID:
NCT06290817
Condition:
Diffuse Large B-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Orelabrutinib combined with R-CDOP regimen
Description:
All participants were treated with the orelabrutinib combined with R-CHOP regimen
(O-RCDOP). The treatment plan involved orelabrutinib tablets at 150mg QD (once daily)
from day 1 to day 21, Rituximab at 375mg/m2 on day 1; Cyclophosphamide at 750mg/m2 on day
1; Liposomal Doxorubicin at 30mg/m2 on day 0; Vincristine at 25mg/m2 on day 1 (maximum
dose 40mg); and Prednisone at 100mg from day 1 to day 5. The treatment cycles were set
every 21 days for a total of 6-8 cycles. Dose adjustments were made for elderly patients
for Cyclophosphamide and Liposomal Doxorubicin based on age: 70-80% of the dose for those
aged 70-80 years old, and 50-60% of the dose for those older than 80 years.
Arm group label:
Orelabrutinib combined with R-CDOP regimen
Summary:
This is a prospective, multicenter, single-arm clinical study on the treatment of newly
diagnosed diffuse large B-cell lymphoma with high-risk of CNS relapse defined by CNS-IPI
using Orelabrutinib in combination with R-CDOP regimen.
Detailed description:
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of B-cell lymphoma, where the
dual expression of Myc and BCL-2 genes in non-germinal center B-cell like (non-GCB)
lymphomas is associated with a poor prognosis when treated with the standard R-CHOP
regimen. Bruton's tyrosine kinase (BTK), a key kinase in the B-cell receptor (BCR)
signaling pathway, is an important target for the treatment of B-cell lymphomas. Studies
have shown that the first-generation BTK inhibitor Ibrutinib when combined with the
R-CHOP regimen for previously untreated patients with dual-expressing, non-GCB lymphomas,
can improve event-free survival rates. Orelabrutinib, as a new generation BTK inhibitor
independently developed in China, possesses higher inhibitory activity against BTK kinase
and can penetrate the blood-brain barrier, offering potential benefits for patients at
high risk of central nervous system relapse. The novel anthracycline drug-Liposomal
Doxorubicin, which has almost no cardiac toxicity, suggests that the combination of
Orelabrutinib with the R-CDOP regimen could improve the adverse prognosis of DLBCL
patients at high risk of central relapse. This is a prospective, multicenter, single-arm
clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with
high-risk CNS-IPI using Orelabrutinib in combination with R-CDOP regimen. All
participants were treated with the Orelabrutinib combined with R-CDOP regimen. The
treatment cycles were set every 21 days for a total of 6-8 cycles. During the study
treatment period, researchers conducted a tumor assessment (with a 1-week time window
allowed) after the screening period and once again after the 4th, 6th, or 8th cycle of
treatment to evaluate the antitumor efficacy of the investigational drug. After all
treatment cycles were completed, follow-up visits were conducted every 3 months until the
end of the 3-year period. The median duration of follow-up was 24 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years old; ECOG score 0-3;
2. Histologically confirmed diffuse large B-cell lymphoma, including DLBCL and
transformed DLBCL;
3. CNS-IPI≥4 points
4. Previously untreated participants with CD20-positive DLBCL,;
5. Heart, liver, and kidney function: creatinine < 2 times the normal upper limit
(ULN); ALT (alanine aminotransferase)/AST (Aspartate Aminotransferase) < 2.5ULN;
Total bilirubin < 2ULN; Cardiac ejection fraction (EF) ≥50%.
6. At least one measurable lesion.
7. Have the sufficient understanding ability and voluntarily sign informed consent.
Exclusion Criteria:
1. Patients with evidence of CNS involvement ;
2. Clinically significant active cardiovascular disease, such as uncontrolled
arrhythmia, uncontrolled hypertension, congestive heart failure, any grade 3 or 4
heart disease as determined by the New York Heart Association (NYHA) functional
scale, or a history of myocardial infarction within 6 months before screening;
3. Human immunodeficiency virus (HIV) infection;
4. Pregnant or lactating women;
5. Other tumors that require treatment;
6. Uncontrolled active infection;
7. The HBV DNA copy number of active hepatitis after antiviral treatment can not be
controlled within 2×103/ml.
8. unable to understand and follow the research protocol or unable to sign the informed
consent.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Address:
City:
Zhejiang
Country:
China
Status:
Recruiting
Contact:
Last name:
Wenbin Qian
Investigator:
Last name:
Xibin Xiao
Email:
Sub-Investigator
Facility:
Name:
Huzhou Central Hospital
Address:
City:
Huzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Lihong Shou
Phone:
13362216921
Email:
SLH077@126.COM
Facility:
Name:
Affiliated hospital of Jiaxing University , the First Hospital of Jiaxing
Address:
City:
Jiaxing
Country:
China
Status:
Recruiting
Contact:
Last name:
Hui Zeng
Phone:
13957330440
Email:
zhwuhqn@163.com
Facility:
Name:
Affiliated hospital of Jiaxing University , the Second Hospital of Jiaxing
Address:
City:
Jiaxing
Country:
China
Status:
Recruiting
Contact:
Last name:
Beili Hu
Phone:
0573-82080930
Email:
87718916@qq.com
Facility:
Name:
Ningbo Medical Center LiHuili Hospital
Address:
City:
Ningbo
Country:
China
Status:
Recruiting
Contact:
Last name:
Jing Le
Phone:
13566511755
Email:
nblejing@aliyun.com
Facility:
Name:
Taizhou Hospital of Zhejiang
Address:
City:
Taizhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Yiqun Guo
Phone:
13515861286
Email:
guoqunyi@163.com
Start date:
March 30, 2023
Completion date:
March 20, 2026
Lead sponsor:
Agency:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Collaborator:
Agency:
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
Agency class:
Other
Collaborator:
Agency:
Huizhou Municipal Central Hospital
Agency class:
Other
Collaborator:
Agency:
Ningbo Medical Center Lihuili Hospital
Agency class:
Other
Collaborator:
Agency:
Affiliated Hospital of Jiaxing University
Agency class:
Other
Collaborator:
Agency:
The Second Affiliated Hospital of Jiaxing University
Agency class:
Other
Source:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06290817
