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

March 1, 2024 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Huzhou, China
        • Recruiting
        • Huzhou Central Hospital
        • Contact:
      • Jiaxing, China
        • Recruiting
        • Affiliated hospital of Jiaxing University , the First Hospital of Jiaxing
        • Contact:
      • Jiaxing, China
        • Recruiting
        • Affiliated hospital of Jiaxing University , the Second Hospital of Jiaxing
        • Contact:
      • Ningbo, China
        • Recruiting
        • Ningbo Medical Center Lihuili Hospital
        • Contact:
      • Taizhou, China
        • Recruiting
        • Taizhou Hospital of Zhejiang
        • Contact:
    • Zhejiang
      • Zhejiang, Zhejiang, China
        • Recruiting
        • Second Affiliated Hospital, School of Medicine, Zhejiang University
        • Contact:
          • WenBin Qian
        • Sub-Investigator:
          • Xibin Xiao

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year central nervous system relapse rate
Time Frame: up to 2 years
The proportion of patients with central nervous system recurrence within two years from enrollment accounted for all patients treated with drugs.
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year progression-free survival (PFS) rate
Time Frame: 2 years after enrollment of final patient
Number of non-progression cases/all enrolled cases at 2 years
2 years after enrollment of final patient
Complete Response Rate
Time Frame: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
The rate of patients who achieved complete response after treatment.
At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
Overall Response Rate (ORR)
Time Frame: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
The rate of patients who achieved CR or PR after treatment.
At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
2-year Overall survival (OS) rate
Time Frame: Up to 2 years
2-year overall survival (OS) rate Accessed by the investigator
Up to 2 years
1-year Overall survival (OS) rate
Time Frame: Up to 1 year
1-year overall survival (OS) rate Accessed by the investigator
Up to 1 year
1-year progression-free survival (PFS) rate
Time Frame: 1 year after enrollment of final patient
Number of non-progression cases/all enrolled cases at 1 year
1 year after enrollment of final patient
Occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03
Time Frame: Up to 3 years
The safety of Orelabrutinib is measured by the occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03
Up to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of adverse events and serious adverse events according to CTCAE V4.03
Time Frame: Up to 3 years
The safety of Orelabrutinib measured by the occurrence of adverse events and serious adverse events according to CTCAE V4.03.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

Ningbo Medical Center Lihuili Hospital
Huizhou Municipal Central Hospital
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
The Second Affiliated Hospital of Jiaxing University
Affiliated Hospital of Jiaxing University

Investigators

  • Study Director: Wenbin Qian, 15.1 Second affiliated hospital， School of Medicine， Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2023

Primary Completion (Estimated)

March 30, 2025

Study Completion (Estimated)

March 20, 2026

Study Registration Dates

First Submitted

February 27, 2024

First Submitted That Met QC Criteria

March 1, 2024

First Posted (Estimated)

March 4, 2024

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-0724

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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