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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 30, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 20, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 27, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2024

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 4, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 4, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings