Study of Tirabrutinib, Rituximab, and Temozolomide in Patients with Relapsed/Refractory Primary Central Nervous System Lymphoma

3 1 1 1

What is this study about?

This study is being done in relapsed/refractory primary central nervous system lymphoma, a type of cancer that starts in the brain, spinal cord, or the tissues around them and has come back or has not improved with earlier treatment. The purpose of the study is to compare tirabrutinib taken by mouth with a treatment made of rituximab and temozolomide. Rituximab is given by infusion, which means it goes into a vein through a needle, and temozolomide is taken by mouth as capsules.

In this study, participants are assigned to one of the treatment groups by chance. One group receives tirabrutinib alone, and the other group receives rituximab plus temozolomide. Treatment is given over a period of time with regular study visits, and health is checked throughout the study to see how the disease responds and how long the disease stays under control. The study also looks at overall survival, which means how long people live after joining the study, and at changes in steroid medicine use.

This is a Phase 3 study, which means the treatment is being compared in a larger group of people to help show how well it works and how safe it is. It is a randomized study, so the treatment group is chosen by chance, and it is open-label, which means both the study team and the participants know which treatment is being given.

1 randomization and start of study treatment

After joining the study, you are randomized, which means you are assigned by chance to one of two treatment groups.

You receive either tirabrutinib taken by mouth as a 480 mg tablet, or rituximab with temozolomide.

The study is open-label, which means you and the study team know which treatment you receive.

2 tirabrutinib treatment course

If you are assigned to tirabrutinib, you take 480 mg by mouth.

The medicine is given as a tablet.

The treatment continues for the period assigned in the study, until the study treatment is stopped according to the trial rules.

3 rituximab and temozolomide treatment course

If you are assigned to the other treatment group, you receive rituximab and temozolomide.

Rituximab is given by intravenous infusion, which means it is delivered into a vein. The dose is 375 mg/m2.

Temozolomide is taken by mouth at a dose of 200 mg/m2.

Temozolomide is provided as hard capsules, including 100 mg, 20 mg, and 5 mg strengths.

The treatment continues for the period assigned in the study, until the study treatment is stopped according to the trial rules.

4 study follow-up and response checks

During the trial, your condition is checked to see whether the disease gets worse, stays stable, or improves.

The main measure is progression-free survival, or PFS. This means the length of time from randomization until the disease gets worse or death occurs, whichever happens first.

The study also checks how many people have a response to treatment, how long it takes to respond, how long a response lasts, and overall survival, which means the time from randomization until death from any cause.

If you are taking corticosteroids, the study also tracks changes in the dose. Corticosteroids are medicines that reduce swelling and inflammation.

5 end of treatment assessment

At the end of the treatment period, your disease status and treatment response are assessed again.

The study records whether there has been a complete response, partial response, or disease progression.

The trial then continues to use these results for the planned study outcomes.

6 study duration

The study is planned to run from 2026-05-30 to 2029-10-15.

Who Can Join the Study?

Written informed consent must be provided by the participant or by a legally authorized representative before screening. Informed consent means agreeing to join the study after the study has been explained.
A pathology report must confirm the diagnosis of B-cell primary central nervous system lymphoma (B-cell PCNSL). A pathology report is a laboratory report that examines tissue to confirm the diagnosis.
The lymphoma must be relapsed or refractory B-cell PCNSL, and the participant must have had at least 1 previous treatment based on high-dose methotrexate (HD-MTX). High-dose methotrexate is a chemotherapy medicine given in a higher amount than usual.
If the disease is relapsed, the participant must have responded to the last treatment with complete response (CR), complete response unconfirmed (CRu), or partial response (PR), and then later had the disease get worse again. These terms mean the cancer disappeared completely, almost completely, or shrank, before returning.
If the disease is refractory, the participant’s best response to the last treatment must have been stable disease or progressive disease (PD). Stable disease means the cancer did not clearly shrink or grow. Progressive disease means it got worse.
The participant must have 1 or more measurable brain lesions on gadolinium-enhanced MRI that are at least 1 cm by 1 cm in size. A lesion is an abnormal area, and MRI is a scan that makes detailed pictures of the brain. Gadolinium is a contrast dye used to make the lesion easier to see.
The participant must have an ECOG performance status of 0 to 2. This is a scale that shows how well a person can do daily activities. A score of 0 means fully active, and 2 means able to do self-care but unable to do work activities.
The participant must have adequate bone marrow, kidney, and liver function based on central laboratory results. Adequate means the organs are working well enough for study treatment.
The participant must agree to follow all required contraception rules. Contraception means methods used to prevent pregnancy.
The participant must be a patient in the age group allowed for the study.

Who Cannot Join the Study?

People with only eye disease from this lymphoma, or only spinal cord disease with no brain lesions (no tumors or abnormal areas in the brain).
People with non-B-cell lymphoma in the central nervous system. B cells are a type of white blood cell.
People who have lymphoma outside the central nervous system at the same time. This means the lymphoma is also present in other parts of the body.
People whose last treatment for this lymphoma did not work against temozolomide, with or without rituximab. Refractory means the cancer does not respond to treatment.
People who used systemic corticosteroids within 14 days before starting the study drug, unless the dose is within the allowed limits. Corticosteroids are medicines that reduce swelling and inflammation and work throughout the whole body.
People with another active cancer that needs treatment throughout the body, other than this lymphoma.
People with other poorly controlled medical conditions, or any medical history that the study doctor considers unsafe for participation.
People who are unable to swallow oral medicine by mouth.
People who have had a Bruton’s tyrosine kinase inhibitor before. This is a type of medicine that blocks a protein used by certain cancer cells to grow.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
IRCCS Humanitas Research Hospital	Rozzano	Italy
Medical University Of Vienna	Vienna	Austria
Universitaetsmedizin Goettingen	Goettingen	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany
Pomeranian Medical University	Szczecin	Poland
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Aix Marseille University	Marseille	France
Azienda Ospedaliero Universitaria Di Sassari	Sassari	Italy

Other Sites

Site Name	City	Country
Klinikum Oldenburg AöR	Oldenburg In Holstein	Germany
University Hospital Ostrava	Ostrava	Czechia
Hospital Clinic De Barcelona	Barcelona	Spain
Fakultni Nemocnice Kralovske Vinohrady	Prague	Czechia
Centre Hospitalier Universitaire De Montpellier	Montpellier	France
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie	Cracow	Poland
Vseobecna Fakultni Nemocnice V Praze	Prague	Czechia
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Hospital Universitario 12 De Octubre	Madrid	Spain
Universita Degli Studi Di Brescia	Brescia	Italy
Cictormua Utydpdxtosyuao Srabrujkc	Woluwe-Saint-Lambert	Belgium
Hkamyona Vwcw dixksxlb	Barcelona	Spain
Ijxrcqww Rtmcjgyxv Pzu Lb Sukhol Drt Ttfltx Dlhu Ajwlgmd Icce Ssinpd	Meldola	Italy
Awlnjou Odjyzioudao Ulvxidliwibpe Syxuak	Siena	Italy
Cgsykk Hpdfwzlybjj Rwzgudxe Uctxbhebgocfm Dd Tpdth	Tours	France
Ahytxuk Oeuxlytmkck Ulohtvoqeoncy Cxlpzdqivowp Dknre Sivsie E Dovmy Stkfwgg Dr Teoeec	Turin	Italy
Nqbxqanr Ihslgfhc Oznispizq Iwt Mmxct Sxadialgpbihifbioonbhnntmafb Ieqzzbqv Buweexrj	Cracow	Poland
Uhovxdllqhqpsohohnpje Wrvffxoon Ads	Wuerzburg	Germany
Ahngbss Ujs Ijtnz Dg Rsxmhj Eflnpi	Reggio Emilia	Italy
Uakmvkfzgvloee Cvuftim Kjqigbyov	Gdansk	Poland
Azawlqo Ouqmjkexmrc Penf Grbrogjk Xfupg	Bergamo	Italy
Mydyqlrctobmbkwdivedqitzqz Hmuljpvhuqjtmndj	Halle (Saale)	Germany
Ijpqjmne Cybcer Dwqmejxunqicladrl	L'hospitalet De Llobregat	Spain
Wpskmawympz Wuazecjazxbzeogcrikn Cnsonpg Odossfjri I Tjckjqgaecwnf Ih Mhdwphgagrr W Lghzv	Lodz	Poland

Trial status

Country	Status	Recruitment Start
Austria	Not yet recruiting	30.05.2026
Belgium	Not yet recruiting	30.05.2026
Czechia	Not yet recruiting	30.05.2026
France	Not yet recruiting	30.05.2026
Germany	Not yet recruiting	30.05.2026
Italy	Not yet recruiting	30.05.2026
Poland	Not yet recruiting	30.05.2026
Spain	Not yet recruiting	30.05.2026

Trial locations

Investigated drugs:

Tirabrutinib is an oral tablet used by itself in this study. It is the main treatment being tested, and researchers want to see how well it works for people with relapsed or hard-to-treat primary central nervous system lymphoma.

Rituximab is given as an infusion into a vein. In this trial, it is part of the comparison treatment and is used together with temozolomide. It helps the body’s immune system target lymphoma cells.

Temozolomide is an oral capsule used as part of the comparison treatment with rituximab. It is a chemotherapy medicine that helps kill or slow the growth of lymphoma cells.

Relapsed/refractory primary central nervous system lymphoma – A type of lymphoma that starts in the brain, spinal cord, or nearby tissues and has returned after treatment or has not responded to treatment. It usually grows by forming one or more masses in the central nervous system and may slowly worsen over time. Symptoms can develop as the tumor spreads within the brain or spinal cord and affects nearby tissue.

Trial ID:

2025-523389-26-00

Protocol code:

ONO-4059-17

NCT ID:

NCT07104032

Trial Phase:

Therapeutic confirmatory (Phase III)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Study of Tirabrutinib, Rituximab, and Temozolomide in Patients with Relapsed/Refractory Primary Central Nervous System Lymphoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?