Primary Central Nervous System LymphomaPhase 2TIMELY-pIINCT06940791
Tirabrutinib Maintenance Versus Placebo in Patients With Primary CNS Lymphoma in Complete Remission (JCOG2104)
A Phase 2 study testing Tirabrutinib in people with Primary Central Nervous System Lymphoma, run by Kyorin University at 1 site in Japan.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Central Nervous System Lymphoma
- What is being tested?
- Tirabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteJapan
- Study dates
- 6 Oct 2023to Feb 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathological diagnosis of B cell lymphoma.
- Newly-diagnosed PCNSL confined to the cerebrum, cerebellum and brainstem. Patients with or without interocular lymphoma are eligible.
- 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.
- 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.
- Patients with a single lesion, or multiple lesions, are eligible.
- Patients 18 years old or older at the time of registration.
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- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, 2.
- 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
- Complete response (CR) or complete response unconfirmed (CRu) based on the International PCNSL Collaborative Group (IPCG) criteria.
- Within 60 days from the last dose of induction or consolidation chemotherapy.
- No treatment history of radiotherapy for PCNSL.
- Refused to receive consolidation radiotherapy.
- No treatment history of chemotherapy or radiotherapy, except for stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) for non-cancer diseases (such as arteriovenous malformations).
- 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
- Written informed consent.
Who cannot join
- Synchronous or metachronous malignancies.
- Infections requiring systemic treatment at the time of registration.
- Body temperature >=38 degree celsius at the time of registration.
- Serious lung disorders, such as interstitial pneumonia, obstructive lung disease, hypersensitive pneumonitis, symptomatic bronchospasm) at the time of registration.
- History or presence of aspergillus pneumonitis or pneumocystis pneumonia.
- History of serious drug allergy or serious anaphylaxis.
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- 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.
- Treated by anticoagulants at the time of registration.
- Treated by antiplatelets at the time of registration.
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
- Immune deficiency, such as acquired immunodeficiency syndrome (AIDS), X-linked agammaglobulinemia, chronic granulomatous disease, Wiskott-Aldrich syndrome, or any other iatrogenic immunosuppressive conditions.
- Post organ transplant immunosuppression.
- Prednisone use of >10 mg/day for condition other than intracranial tumor, or regular use of immunosuppressants.
- Uncontrolled diabetes mellitus.
- Treated either by CYP3A4 inhibitors, CYP3A4 inducers, or P-gp inducers within 14 days prior to registration.
- Gadolinium allergy.
- Positive HIV antibody.
- Positive HBs antigen.
- Positive HBs antibody or HBc antibody, and HBV-DNA positive.
- Positive HCV antibody.
- Unable to take oral medicine,
- Females during pregnancy, or within 28 days postpartum, or during lactation. Males who wish childbearing of his partner.
- Prior history of treatment by BTK inhibitors.
- Severe psychiatric disorders.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Japan1 site, 1 recruiting
- Recruiting
Kyorin University Hospital
Tokyo, 181-8611
Motoo Nagane, M.D., Ph.D., +81-422-47-5511, mnagane@ks.kyorin-u.ac.jp
Nobuyoshi Sasaki, M.D., Ph.D., +81-422-47-5511, sasakinobuyoshi0308@gmail.com
About this study
Official title: Tirabrutinib Maintenance Versus Placebo in Patients With Primary Central Nervous System Lymphoma in Complete Remission: a Randomized Phase II Study (JCOG2104)
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:
Read more
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.
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Tirabrutinib, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirabrutinibDrug
Tirabrutinib (480 mg) taken orally daily at fasting condition
PlaceboDrug
Placebo taken orally daily at fasting condition
| Study group | Role | What they receive |
|---|---|---|
| Standard arm | Placebo comparator | Observation with placebo Receives: Drug: Placebo |
| Experimental arm | Experimental | Tirabrutinib maintenance therapy Receives: Drug: Tirabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) based on independent review committee (IRC) assessment
Measured: From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months
Secondary outcomes (7)
Progression-free survival (PFS) determined by investigator
Measured: From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months
Overall survival (OS)
Measured: From the date of registration until the date of death from any cause, assessed up to 78 months
PFS/OS in the maintenance per protocol group
Measured: PFS: From the date of registration until the date of first progression or date of death from any cause, whichever came first, assessed up to 78 months. OS: From the date of registration until the date of death from any cause, assessed up to 78 months.
PFS/OS by the induction therapy regimen with or without consolidation therapy
Measured: PFS: From the date of registration until the date of first progression or date of death from any cause, whichever came first, assessed up to 78 months. OS: From the date of registration until the date of death from any cause, assessed up to 78 months.
Incidence rate of adverse events
The proportion of patients who experienced each adverse event
Measured: During the intervention up to 78 months, or for those who discontinued the intervention, assessed until 30 days after the last date of intervention or the date of initiation of post-study therapy, whichever came first, assessed up to 78 months.
Proportion of patients without neurological cognitive function (NCF) deterioration
Measured: Among patients eligible for NCF assessment, the proportion without deterioration in each assessment item at the following time points: pre-treatment baseline (after registration but before initiation of the study treatment), 48 weeks, 2 years, and 3 year
Proportion of patients without deterioration in health-related QOL
Measured: Among patients eligible for HR-QOL assessment, the proportion without deterioration at the following time points: pre-treatment baseline (after registration but before initiation of the study treatment), 48 weeks, 2 years, and 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2025
- Study start6 Oct 2023
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kyorin University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Center, Japan, Ono Pharmaceutical Co., Ltd., Japan Clinical Oncology Group
- Responsible party
- Principal investigator, Motoo Nagane, Kyorin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06940791
- Sponsor's protocol ID
- JCOG2104
- Acronym
- TIMELY-pII
- Status last verified
- Aug 2026
- First submitted
- 4 Apr 2025
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tirabrutinib Maintenance Versus Placebo in Patients With Primary Central Nervous System Lymphoma in Complete Remission: a Randomized Phase II Study (JCOG2104)
- ClinicalTrials.gov ID
- NCT06940791
- Acronym / sponsor ID
- TIMELY-pII / JCOG2104
- Conditions
- Primary Central Nervous System Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Kyorin UniversityUniversity, hospital or other
- Collaborators
- National Cancer Center, Japan, Ono Pharmaceutical Co., Ltd., Japan Clinical Oncology Group
- Study start
- 6 Oct 2023 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 23 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard arm | Placebo comparator | Drug: PlaceboObservation with placebo |
| Experimental arm | Experimental | Drug: TirabrutinibTirabrutinib maintenance therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histopathological diagnosis of B cell lymphoma.
- Newly-diagnosed PCNSL confined to the cerebrum, cerebellum and brainstem. Patients with or without interocular lymphoma are eligible.
- 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.
- 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.
- Patients with a single lesion, or multiple lesions, are eligible.
Key exclusion criteria (24 listed)
- Synchronous or metachronous malignancies.
- Infections requiring systemic treatment at the time of registration.
- Body temperature >=38 degree celsius at the time of registration.
- Serious lung disorders, such as interstitial pneumonia, obstructive lung disease, hypersensitive pneumonitis, symptomatic bronchospasm) at the time of registration.
- History or presence of aspergillus pneumonitis or pneumocystis pneumonia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirabrutinibTirabrutinib (480 mg) taken orally daily at fasting condition | Drug | Experimental arm |
| PlaceboPlacebo taken orally daily at fasting condition | Drug | Standard arm |
Primary outcome
Progression-free survival (PFS) based on independent review committee (IRC) assessment
Time frame: From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months
7 secondary outcomes
Progression-free survival (PFS) determined by investigator
Time frame: From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months
Overall survival (OS)
Time frame: From the date of registration until the date of death from any cause, assessed up to 78 months
PFS/OS in the maintenance per protocol group
Time frame: PFS: From the date of registration until the date of first progression or date of death from any cause, whichever came first, assessed up to 78 months. OS: From the date of registration until the date of death from any cause, assessed up to 78 months.
PFS/OS by the induction therapy regimen with or without consolidation therapy
Time frame: PFS: From the date of registration until the date of first progression or date of death from any cause, whichever came first, assessed up to 78 months. OS: From the date of registration until the date of death from any cause, assessed up to 78 months.
Incidence rate of adverse events
Time frame: During the intervention up to 78 months, or for those who discontinued the intervention, assessed until 30 days after the last date of intervention or the date of initiation of post-study therapy, whichever came first, assessed up to 78 months.
Proportion of patients without neurological cognitive function (NCF) deterioration
Time frame: Among patients eligible for NCF assessment, the proportion without deterioration in each assessment item at the following time points: pre-treatment baseline (after registration but before initiation of the study treatment), 48 weeks, 2 years, and 3 year
Proportion of patients without deterioration in health-related QOL
Time frame: Among patients eligible for HR-QOL assessment, the proportion without deterioration at the following time points: pre-treatment baseline (after registration but before initiation of the study treatment), 48 weeks, 2 years, and 3 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirabrutinib in people with Primary Central Nervous System Lymphoma, run by Kyorin University at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nobuyoshi Sasaki, M.D., Ph.D. (+81422475511, sasakinobuyoshi0308@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) based on independent review committee (IRC) assessment (time frame: From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2026.