Tirabrutinib Maintenance Versus Placebo in Patients With Primary CNS Lymphoma in Complete Remission (JCOG2104)

NCT ID: NCT06940791

Last Updated: 2025-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

92 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-06

Study Completion Date

2030-02-28

Brief Summary

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A double-blind, randomized phase II comparative trial will evaluate the superiority of the investigational treatment (tirabrutinib maintenance therapy) over standard care (observation with placebo) in terms of progression-free survival in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) who have achieved complete response (CR or CRu) following induction therapy with high-dose methotrexate (HD-MTX)-based chemotherapy and have not undergone consolidative whole-brain irradiation.

Participants will:

Take protocol drug tirabrutinib or a placebo every day until disease progression or experience of unacceptable toxicity.

Visit the clinic once every 4 weeks for checkups and tests, as well as protocol drug prescription.

Detailed Description

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Conditions

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Primary Central Nervous System Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Standard arm

Observation with placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo taken orally daily at fasting condition

Experimental arm

Tirabrutinib maintenance therapy

Group Type EXPERIMENTAL

Tirabrutinib

Intervention Type DRUG

Tirabrutinib (480 mg) taken orally daily at fasting condition

Interventions

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Tirabrutinib

Tirabrutinib (480 mg) taken orally daily at fasting condition

Intervention Type DRUG

Placebo

Placebo taken orally daily at fasting condition

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histopathological diagnosis of B cell lymphoma.
2. Newly-diagnosed PCNSL confined to the cerebrum, cerebellum and brainstem. Patients with or without interocular lymphoma are eligible.
3. Negative cerebrospinal fluid (CSF) cytology, or no evidence of leptomeningeal lymphomatosis in contrast-enhanced magnetic resonance imaging (MRI) of the brain and the whole spinal cord.
4. No evidence of systemic lymphoma before induction chemotherapy, confirmed by contrast-enhanced CT including the neck, chest, abdomen, pelvic cavity and groin, or whole-body positron-emission tomography (PET) and CT.
5. Patients with a single lesion, or multiple lesions, are eligible.
6. Patients 18 years old or older at the time of registration.
7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, 2.
8. Have completed either of the following methotrexate (MTX)-based chemotherapy i) R-MPV (rituximab, MTX, procarbazine and vincristine) ii) MPV (MTX, procarbazine and vincristine) iii) R-MP (rituximab, MTX and procarbazine) iv) MP (MTX and procarbazine) v) R-M (rituximab and MTX) vi) MTX monotherapy
9. Complete response (CR) or complete response unconfirmed (CRu) based on the International PCNSL Collaborative Group (IPCG) criteria.
10. Within 60 days from the last dose of induction or consolidation chemotherapy.
11. No treatment history of radiotherapy for PCNSL.
12. Refused to receive consolidation radiotherapy.
13. No treatment history of chemotherapy or radiotherapy, except for stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) for non-cancer diseases (such as arteriovenous malformations).
14. Adequate organ function. i) Neutrophil count \>=1,000/mm3 ii) Hemoglobin \>= 8.0 g/dl iii) Platelet count \>= 75,000/mm3 iv) AST \<=120 U/L v) ALT \<= 120 U/L vi) Total Bilirubin \<= 2.25 mg/dl vii) Creatinine \<= 1.5 mg/dL
15. Written informed consent.

Exclusion Criteria

1. Synchronous or metachronous malignancies.
2. Infections requiring systemic treatment at the time of registration.
3. Body temperature \>=38 degree celsius at the time of registration.
4. Serious lung disorders, such as interstitial pneumonia, obstructive lung disease, hypersensitive pneumonitis, symptomatic bronchospasm) at the time of registration.
5. History or presence of aspergillus pneumonitis or pneumocystis pneumonia.
6. History of serious drug allergy or serious anaphylaxis.
7. Heart failure (\>= III in New York Heart Association functional classification), unstable angina pectoris, or history of myocardial infarction within the preceding 180 days prior to registration.
8. Treated by anticoagulants at the time of registration.
9. Treated by antiplatelets at the time of registration.
10. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
11. Immune deficiency, such as acquired immunodeficiency syndrome (AIDS), X-linked agammaglobulinemia, chronic granulomatous disease, Wiskott-Aldrich syndrome, or any other iatrogenic immunosuppressive conditions.
12. Post organ transplant immunosuppression.
13. Prednisone use of \>10 mg/day for condition other than intracranial tumor, or regular use of immunosuppressants.
14. Uncontrolled diabetes mellitus.
15. Treated either by CYP3A4 inhibitors, CYP3A4 inducers, or P-gp inducers within 14 days prior to registration.
16. Gadolinium allergy.
17. Positive HIV antibody.
18. Positive HBs antigen.
19. Positive HBs antibody or HBc antibody, and HBV-DNA positive.
20. Positive HCV antibody.
21. Unable to take oral medicine,
22. Females during pregnancy, or within 28 days postpartum, or during lactation. Males who wish childbearing of his partner.
23. Prior history of treatment by BTK inhibitors.
24. Severe psychiatric disorders.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Center, Japan

OTHER_GOV

Sponsor Role collaborator

Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Japan Clinical Oncology Group

OTHER

Sponsor Role collaborator

Kyorin University

OTHER

Sponsor Role lead

Responsible Party

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Motoo Nagane

Professor, Department of Neurosurgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Kyorin University Hospital

Tokyo, , Japan

Site Status RECRUITING

Countries

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Japan

Central Contacts

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Nobuyoshi Sasaki, M.D., Ph.D.

Role: CONTACT

+81422475511

Motoo Nagane, M.D., Ph.D.

Role: CONTACT

+81422475511

Facility Contacts

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Motoo Nagane, M.D., Ph.D.

Role: primary

+81-422-47-5511

Nobuyoshi Sasaki, M.D., Ph.D.

Role: backup

+81-422-47-5511

Other Identifiers

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JCOG2104

Identifier Type: -

Identifier Source: org_study_id

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