Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study)

Exclusion Criteria (Part A) – Closed to enrollment

• Intraocular (within the eye) PCNSL with no brain lesion
• Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
• Patient with non-B cell PCNSL
• Patient with systemic presence of lymphoma
• 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
• Prior BTK inhibitor treatment
• 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
• Taking a 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
• Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
• Taking 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
• Active malignancy, other than PCNSL requiring systemic therapy
• Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
• Patient with bleeding disorder
• Patients with a history of moderate or severe liver impairment
• QTcF (heart rate measurement) > 480 milliseconds or requirement for ongoing treatment with medications that prolong the QT interval
• 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
• Prior history of hypersensitivity or anaphylaxis to tirabrutinib
• Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
• Medical history of organ tissue graft
• 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.
• 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.
• Women who are pregnant or lactating
• Patient is found incapable of giving consent due to dementia or another such condition
• Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator.

Exclusion Criteria (Part B)

• Intraocular (within the eye) PCNSL with no brain lesion
• 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
• Patients with a history of intolerable toxicity, hypersensitivity, or anaphylaxis to the selected backbone regimen medications
• Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
• Patient with non-B cell PCNSL
• Patient with systemic presence of lymphoma
• 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
• Prior BTK inhibitor treatment
• 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
• Taking 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
• Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
• Taking 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
• Active malignancy, other than PCNSL requiring systemic therapy
• Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
• Patient with bleeding disorder
• Patients with a history of moderate or severe liver impairment
• QTcF (heart rate measurement) > 480 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval
• 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
• Prior history of hypersensitivity or anaphylaxis to tirabrutinib
• Prior history of Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
• Medical history of organ tissue grafts
• 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.
• Patient is unable to swallow tablets; has malabsorption, malabsorption syndrome, or a comorbidity that affects stomach 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.
• Women who are pregnant or lactating
• Patient is found incapable of giving consent due to dementia or another such condition
• Patient is found to be otherwise ineligible for the study by the Investigator or sub-Investigator