Clinical trial NCT06290817: Orelabrutinib Combined With R-CDOP for DLBCL Patients With High-risk of CNS Relapse Defined by CNS-IPI
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
name: Huizhou Municipal Central Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Affiliated Hospital of Jiaxing University
name: The Second Affiliated Hospital of Jiaxing University
First posted: 2024-03-04
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 2-year central nervous system relapse rate
timeFrame: up to 2 years
Secondary outcomes:
measure: Complete Response Rate
timeFrame: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
measure: Overall Response Rate (ORR)
timeFrame: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
measure: 2-year Overall survival (OS) rate
timeFrame: Up to 2 years
measure: 1-year Overall survival (OS) rate
timeFrame: Up to 1 year
measure: 2-year progression-free survival (PFS) rate
timeFrame: 2 years after enrollment of final patient
measure: 1-year progression-free survival (PFS) rate
timeFrame: 1 year after enrollment of final patient
measure: Occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03
timeFrame: Up to 3 years
Other outcomes:
measure: Occurrence of adverse events and serious adverse events according to CTCAE V4.03
timeFrame: Up to 3 years
Locations:
city: Zhejiang
country: China
facility: Second Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
city: Huzhou
country: China
facility: Huzhou Central Hospital
city: Jiaxing
country: China
facility: Affiliated hospital of Jiaxing University , the First Hospital of Jiaxing
city: Jiaxing
country: China
facility: Affiliated hospital of Jiaxing University , the Second Hospital of Jiaxing
city: Ningbo
country: China
facility: Ningbo Medical Center LiHuili Hospital
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang
Study officials:
affiliation: 15.1 Second affiliated hospital， School of Medicine， Zhejiang University
name: Wenbin Qian
role: STUDY_DIRECTOR
References: