Real-World Evidence of Effectiveness and Safety of Tirabrutinib in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma in Taiwan: A Nationwide Study (REVEAL)

The goal of this observational study is to describe the real-world effectiveness and safety of tirabrutinib among relapsed or refractory PCNSL patients in Taiwan.

Study Overview

• Status: Completed
• Conditions: Primary Central Nervous System Lymphoma (PCNSL)

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung City, Taiwan
    • Chang Gung Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung Univeristy Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients received Taiwan NHI reimbursement

Description

Inclusion Criteria:

1. Patient is ≥ 18 years of age.
2. r/r PCNSL patient, who has newly started NHI public reimbursement tirabrutinib from 01 June 2024 to 30 June 2025.
3. Have provided voluntary written consent, directly from the subject, or through his/her legal representative for a patient who lacks the capacity to give informed consent.
4. Deceased patients are considered included under an IRB-approved consent waiver.

Note: The NHI reimbursement criteria are listed below for reference purposes only. Subject enrollment depends on whether reimbursement has been received.

1. Histopathologically confirmed large B-cell PCNSL.
2. Patients with relapsed or refractory PCNSL previously treated at least 2 cycles of HD-MTX.
3. Exclude HIV infection
4. Exclude Burkitt lymphoma
5. Exclude patients using chemotherapy or monoclonal antibodies at the initiation of tirabrutinib treatment.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	objective response rate is defined as the proportion of subjects who respond either Complete response (CR), Partial response (PR), or unconfirmed Complete response (CRu) to therapy, according to International PCNSL Collaborative Group (IPCG) criteria.	At least 9 months for each subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Duration of response is defined as the time from onset of response* to disease progression or death, wichever occurs earlier. *for patients who achieve complete response (CR), partial response (PR), or unconfirmed complete response (CRu), according to IPCG criteria.	At least 9 months for each subject
Time-to-treatment response (TTR)	Time-to-treatment response was defined as time from newly started tirabrutinib treatment to the first objective tumor response observed for patients who achieved a complete response (CR), partial response (PR), or unconfirmed complete response (CRu), according to IPCG criteria.	At least 9 months for each subject
Adverse events of special interest (AESIs)	Drug-related adverse events for treatment interruption, dose reduction, and discontinuation of tirabrutinib: febrile neutropenia (grade≥3), thrombocytopenia with hemorrhage (grade 3), neutropenia (grade 4), thrombocytopenia (grade 4), interstitial lung disease (grade≥2), skin disorder (grade≥2), hematotoxicity (grade≥3, other than events described above) and nonhematological toxicity (other than interstitial lung disease and skin disorder, grade≥3) (the grading will be according to CTCAE v5.0.) important identified risks: infection, severe skin disorder, bone marrow depression, hypersensitivity, interstitial lung disease (ILD), hepatic dysfunction, hemorrhage, arrhythmia.	At least 9 months for each subject
Clinical laboratory test	Clinical laboratory tests (hematology, blood biochemistry, urinalysis, etc.) will be summarized with dexcriptive statistics. The change from baseline will be presented also, if possible.	At least 9 months for each subject
Treatment-emergent adverse events (TEAEs)	in this study, an AE is defined as any unfavorable or unintended injury/disease or sign (including an abnormal laboratory finding) in a subject administered tirabrutinib, regardless of causality. AE also includes suspected transmission of infectious agents by tirabrutinib. TEAE is defined as an AE that began after the start of tirabrutinib treatment. Concurrent disease at the start of tirabrutinib treatment that has worsened during tirabrutinib treatment for the subject is also included. worsening of the primary disease is not an TEAE. all severity of AEs will be graded according to CTCAE v5.0. All AE that are not considered serious AE are not-serious AE.	At least 9 months for each subject
Overall survival (OS)	overall survival is defined as time from newly started tirabrutinib treatment to death.	At least 9 months for each subject
Progression-free survival (PFS)	Progression-free survival is defined as time from newly started tirabrutinib treatment to either first evidence of progression disease (PD), according to IPCG criteria, or death.	At least 9 months for each subject

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ECOG Performance Status Scale	the ECOG performance status scale was developed by the Eastern Cooperative Oncology Group, now the ECOG-ACRIN Cancer Research Group, and published in 1982. From Grade 0 fully active, able to carry on all pre-disease performance without restriction, to Grade 5 Dead. ECOG performance status scale will be listed and summarized by number and percentage by scoring categories.	At least 9 months for each subject
Clinical usage and pattern of tirabrutinib	For the clinical usage and pattern of tirabrutinib, exposure duration and daily dose for tirabrutinib during study period will be listed for each subject and summarized with descriptive statistics.	At least 9 months for each subject
Ratio of the premedications for infection and skin-related disorders	the premedications for infection and skin-related disorders will be listed and tabulated with number and percentage.	At least 9 months for each subject

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Actual): March 31, 2026
• Study Completion (Actual): March 31, 2026

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 28, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Lymphoma; Brain tumor; Rare disease; PCNSL; REVEAL study; Primary central system lymphoma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Nervous System Neoplasms; Central Nervous System Neoplasms; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Lymphoma; Rare Diseases; Brain Neoplasms
• Other Study ID Numbers: R1128-TIR-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No