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Evaluating Tirabrutinib for Patients with Primary Central Nervous System Lymphoma

An Open-label Phase II Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Tirabrutinib in Patients With Primary Central Nervous System Lymphoma (PCNSL)

Phase 2 Interventional Ono Pharmaceutical Co. Ltd · NCT04947319

This study is testing a new drug called tirabrutinib to see if it helps people with primary central nervous system lymphoma who have either just been diagnosed or have not responded to previous treatments.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment112 (estimated)
Ages18 Years and up
SexAll
SponsorOno Pharmaceutical Co. Ltd Industry-sponsored
Drugs / interventionsrituximab, tirabrutinib, chemotherapy, methotrexate, prednisone
Locations45 sites (Birmingham, Alabama and 44 other locations)
Trial IDNCT04947319 on ClinicalTrials.gov

What this trial studies

This study assesses the effectiveness and safety of tirabrutinib, a Bruton's Tyrosine Kinase Inhibitor, in patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) and those newly diagnosed with the condition. It consists of two parts: Part A focuses on patients who have previously undergone treatment, while Part B examines the drug in combination with high-dose methotrexate regimens for treatment-naïve patients. The study will monitor pharmacokinetics and patient outcomes to determine the potential benefits of tirabrutinib in this challenging patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of primary central nervous system lymphoma, either relapsed or newly diagnosed.

Not a fit: Patients with non-CNS lymphoma or those who have received prior anti-tumor treatments for PCNSL may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients suffering from a difficult-to-treat form of lymphoma.

How similar studies have performed: While the use of Bruton's Tyrosine Kinase Inhibitors is a novel approach in treating PCNSL, similar studies have shown promise in other hematological malignancies.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria (Part A)

1. Written informed consent by the patient prior to screening
2. Patients aged ≥ 18 years on the day of consenting to the study
3. Pathologic diagnosis of PCNSL
4. Relapse or refractory PCNSL with at least one prior high dose methotrexate (HD-MTX) based therapy for PCNSL
5. Measurable brain lesion with a minimum diameter \> 1.0 cm in gadolinium enhanced magnetic resonance imaging (MRI) performed within 14 days before starting tirabrutinib treatment
6. Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1 or 2
7. Life expectancy of at least 3 months
8. Adequate bone marrow, renal, and hepatic function

Inclusion Criteria (Part B)

1. Written informed consent by the patient prior to screening
2. Patients aged ≥ 18 years on the day of consenting to the study
3. Pathologic diagnosis of PCNSL within the past 3 months
4. No prior anti-tumor treatments for PCNSL
5. Patients who, in the opinion of the Investigator, are suitable to receive treatment with a high dose methotrexate containing regimen
6. Measurable brain lesion with a minimum diameter \> 1.0 cm in gadolinium enhanced MRI performed within 14 days before starting study treatment
7. ECOG PS of 0, 1 or 2
8. Life expectancy of at least 6 months
9. Adequate bone marrow, renal, and hepatic function

Exclusion Criteria (Part A)

1. Intraocular PCNSL with no brain lesion
2. Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
3. Patient with non-B cell PCNSL
4. Patient with systemic presence of lymphoma
5. Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment
6. Prior BTK inhibitor treatment
7. Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment
8. Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following:

   * Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL
   * Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both
9. Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
10. Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment
11. Active malignancy, other than PCNSL requiring systemic therapy
12. Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
13. Patient with bleeding diathesis
14. Patients with a history of moderate or severe hepatic impairment
15. QTcF \> 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval
16. Active infection, including a HIV, cytomegalovirus infection or SARS-CoV-2, or has had, within 28 days before starting tirabrutinib treatment, an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic
17. Prior history of hypersensitivity or anaphylaxis to tirabrutinib
18. Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
19. Medical history of organ allografts
20. Tests positive for HIV-1 antibody and HIV-2 antibody, human T-lymphotropic virus 1 antibody, hepatitis B (HB) antigen, or hepatitis C virus (HCV) antibody. Tests positive for HBs antibody or hepatitis B virus core protein antibody and has a result of at least detectable in a hepatitis B virus deoxyribonucleic acid assay despite testing negative for HBs antigen.
21. Patient is unable to swallow tablets; has malabsorption, malabsorption syndrome, or a comorbidity that affects gastric function; has undergone complete resection of the stomach or small intestine; has ulcerative colitis or symptomatic inflammatory bowel disease; or has partial or complete intestinal obstruction.
22. Women who are pregnant or lactating
23. Patient is found incapable of giving consent due to dementia or another such condition
24. Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator.

Exclusion Criteria (Part B)

1. Intraocular PCNSL with no brain lesion
2. Patients for whom the selected backbone regimen medications (i.e, methotrexate/temozolomide/rituximab for MTR and rituximab/methotrexate/procarbazine/vincristine for R-MPV) are contraindicated
3. Patients with a history of intolerable toxicity, hypersensitivity, anaphylaxis to the selected backbone regimen medications
4. Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
5. Patient with non-B cell PCNSL
6. Patient with systemic presence of lymphoma
7. Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment
8. Prior BTK inhibitor treatment
9. Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment
10. Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following:

    * Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL
    * Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both
11. Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
12. Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment
13. Active malignancy, other than PCNSL requiring systemic therapy
14. Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
15. Patient with bleeding diathesis
16. Patients with a history of moderate or severe hepatic impairment
17. QTcF \> 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval
18. Active infection, including a HIV, cytomegalovirus infection or SARS-CoV-2, or has had, within 28 days before starting tirabrutinib treatment, an infection (other than nail trichophytosis) that requires hospitalization or an intravenous antibiotic
19. Prior history of hypersensitivity or anaphylaxis to tirabrutinib
20. Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
21. Medical history of organ allografts
22. Tests positive for HIV-1 antibody and HIV-2 antibody, human T-lymphotropic virus 1 antibody, HBs antigen, or HCV antibody. Tests positive for HBs antibody or hepatitis B virus core protein antibody and has a result of at least detectable in a hepatitis B virus deoxyribonucleic acid assay despite testing negative for HBs antigen.
23. Patient is unable to swallow tablets; has malabsorption, malabsorption syndrome, or a comorbidity that affects gastric function; has undergone complete resection of the stomach or small intestine; has ulcerative colitis or symptomatic inflammatory bowel disease; or has partial or complete intestinal obstruction.
24. Women who are pregnant or lactating
25. Patient is found incapable of giving consent due to dementia or another such condition
26. Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator.

Where this trial is running

Birmingham, Alabama and 44 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Refractory Primary Central Nervous System LymphomaPrimary CNS LymphomaBruton's Tyrosine Kinase Inhibitor, BTKi, tirabrutinib, ONO-4059, PROSPECT
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.