Orelabrutinib Combined With R-CDOP for DLBCL Patients With High-risk of CNS Relapse Defined by CNS-IPI

NCT ID: NCT06290817

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-30
• Study Completion Date: 2026-03-20

Brief 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.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Orelabrutinib combined with R-CDOP regimen

Participants will receive 150 mg of oral orelabrutinib once daily with R-CDOP on day 1 of each cycle (21 days)

Group Type: EXPERIMENTAL

Orelabrutinib combined with R-CDOP regimen

Intervention Type: DRUG

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.

Interventions

Orelabrutinib combined with R-CDOP regimen

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Huizhou Municipal Central Hospital

OTHER

Sponsor Role: collaborator

Ningbo Medical Center Lihuili Hospital

OTHER_GOV

Sponsor Role: collaborator

Affiliated Hospital of Jiaxing University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Jiaxing University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenbin Qian

Role: STUDY_DIRECTOR

15.1 Second affiliated hospital， School of Medicine， Zhejiang University

Locations

Second Affiliated Hospital, School of Medicine, Zhejiang University

Zhejiang, Zhejiang, China

Site Status: RECRUITING

Huzhou Central Hospital

Huzhou, , China

Site Status: RECRUITING

Affiliated hospital of Jiaxing University , the First Hospital of Jiaxing

Jiaxing, , China

Site Status: RECRUITING

Affiliated hospital of Jiaxing University , the Second Hospital of Jiaxing

Jiaxing, , China

Site Status: RECRUITING

Ningbo Medical Center LiHuili Hospital

Ningbo, , China

Site Status: RECRUITING

Taizhou Hospital of Zhejiang

Taizhou, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Xibin Xiao

Role: CONTACT

xiaoxibinzju@zju.edu.cn

13858015535

Facility Contacts

Wenbin Qian

Role: primary

Lihong Shou

Role: primary

SLH077@126.COM

13362216921

Hui Zeng

Role: primary

zhwuhqn@163.com

13957330440

Beili Hu

Role: primary

87718916@qq.com

0573-82080930

Jing Le

Role: primary

nblejing@aliyun.com

13566511755

Yiqun Guo

Role: primary

guoqunyi@163.com

13515861286

Other Identifiers

2023-0724

Identifier Type: -

Identifier Source: org_study_id