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

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: Recruiting
• Conditions: Extranodal Marginal Zone B-cell Lymphoma
• Intervention / Treatment: Drug: Orelabrutinib; Radiation: Ultra-low dose radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jun Shi; Phone Number: 13701867597; Email: junshi@sjtu.edu.cn
• Study Contact Backup: Name: Shaoxin Yang; Phone Number: 18701857626; Email: yangsx19@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
      • Contact: Jun Shi; Phone Number: 13701867597; Email: junshi@sjtu.edu.cn
      • Contact: Shaoxin Yang; Phone Number: 18701857626; Email: yangsx19@163.com

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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

Collaborators and Investigators

• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Investigators: Principal Investigator: Jun Shi, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone
• Other Study ID 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