The Treatment of Ocular Adnexal Extranodal Marginal Zone B-cell Lymphoma by Orelabrutinib and Radiotherapy

July 18, 2024 updated by: Jun Shi, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

The Efficacy of Combination of Orelabrutinib and Ultra-low Dose Radiotherapy in the First-line Treatment of Early Ocular Adnexal Extranodal Marginal Zone B-cell Lymphoma

Extranodal marginal zone B-cell lymphoma (EMZL) is the most common lymphoma of the ocular adnexa (OA), accounting for approximately 60%. As a special part of the body, there is no consensus on the optimal treatment strategy for OA-EMZL. Studies have shown that patients who wait for postoperative observation have a 5-year PFS of approximately 80% and a 10-year PFS of 63%. Therefore, radiotherapy remains an important treatment for stage I/II OA-EMZL patients, but the dosage of radiotherapy remains controversial. In 2014, Hoskin PJ et al. found that the complete response rate and effective rate of patients in the standard 24Gy radiation dose group were 71% and 91%, while those in the 4Gy radiation dose group were 55% and 87%, respectively. Meanwhile, the PFS of patients with 4Gy radiation dose was lower than that of the group with 24Gy radiation dose, but there was no significant difference in OS between the two groups. However, in a study conducted by Chelius M et al. in 2021, they found that the incidence of both early and late toxic effects was significantly higher in the>4Gy radiation dose group than in the<4Gy radiation dose group. These toxic effects inevitably affect the quality of life of patients. Therefore, investigators plan to adopt a combination of ultra-low dose radiotherapy and drug therapy, which not only reduces the side effects of radiotherapy, but also improves the complete response rate of treatment and reduces disease progression or recurrence. However, studies have shown that radiotherapy combined with rituximab cannot improve the disease-specific survival rate of OA-EMZL. Therefore, BTK inhibitors (BTKi), as a novel targeted drug for the treatment of EMZL, have been used to treat relapsed and refractory EZML by interfering with BCR signals. Based on the above research, investigators plan to explore the efficacy of combination therapy with Orelabrutinib and ultra-low dose radiotherapy (4Gy) in the treatment of stage I/II OA-EMZL.

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.

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.
50

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 Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200011
        • Recruiting
        • Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
        • Contact:
        • Contact:

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: Male or female, aged 18-75 years.

    2: Newly diagnosed patients with Marginal Zone B-cell lymphoma of ocular adnexa confirmed by surgical biopsy, with early Ann Arbor stage (stage I/II) and evaluable lesions (> 1cm) on imaging.

    3: Laboratory tests prior to admission must meet the following criteria: white blood cell count ≥3.0x10^9/L, absolute neutrophil count ≥1.5 x10^9/L, hemoglobin ≥90g /L, platelets ≥75x 10^9/L.

Liver function: transaminase levels≤3 times the upper limit of normal, bilirubin levels ≤1.5 times the upper limit of normal.

Serum creatinine clearance ≥30 mL/min. Myocardial enzymes < 2 times the upper limit of normal (same age). ECOG score 0-2.

4: All subjects must provide informed consent and voluntarily sign the written informed consent form themselves or through their legal representatives before participating in the study.

Exclusion Criteria:

  • 1: Pregnant or lactating women, and women of childbearing potential who refuse to use contraceptive measures.

    2: Inability to swallow, chronic diarrhea, or intestinal obstruction, or any condition that affects drug use and absorption.

    3: Pre-trial treatment: Use of drugs that significantly affect the P450 metabolic enzyme pathway within 2 weeks before the screening period.

Current use of cyclosporins or fibrates. Participation in other clinical studies and use of investigational drugs within 28 days prior to the initiation of the study drug.

The need to use concomitant drugs that may prolong QTc or induce tip torsion ventricular TdP, in addition to antimicrobials used as standard care to prevent or treat infections and other such drugs that investigators consider essential for treatment.

4: Evidence of current uncontrolled cardiovascular disease, including: Uncontrolled high blood pressure. Uncontrolled arrhythmia. Symptomatic congestive heart failure. Unstable angina. Myocardial infarction within the past 6 months. Severe acute or chronic infections requiring systemic treatment. Known human immunodeficiency virus (HIV) infection , or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Have a history of uncontrolled seizures, a central nervous system disorder, or a mental illness.

5: History of malignant tumors other than OA-EMZL, unless the patient has been cured for more than 3 years.

6: Any past or current disease, treatment, or laboratory abnormality that may interfere with the study results or affect the subject's full participation in the study, or the investigator deems the subject unfit to participate in the study.

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+Ultra-low dose radiotherapy
Patients will receive radiotherapy 2Gy twice and orelabrutinib orally for 4 months, 150mg Qd
Drug: Orelabrutinib
Orelabrutinib PO will be administered as per the schedule specified in the respective arm
Radiation: Ultra-low dose radiotherapy
2 Gy radiotherapy will be administerd twice in the first cycle

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
Complete Response Rate
Time Frame: End of treatment (4 months after administration)
Percentage of participants with complete response was determined on the basis of investigator assessments
End of treatment (4 months after administration)

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.
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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.
  • Principal Investigator: Jun Shi, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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.
November 1, 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.
October 31, 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.
October 31, 2028

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).
July 10, 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.
July 10, 2024

First Posted (Actual)

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.
July 16, 2024

Study Record Updates

Last Update Posted (Actual)

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.
July 22, 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.
July 18, 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.
July 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.
  • OA-EMZL-1

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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