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

Launched by KYORIN UNIVERSITY · Apr 15, 2025

Keywords

ClinConnect Summary

This clinical trial, called JCOG2104, is studying a new medication called tirabrutinib to see if it can help prevent the return of primary central nervous system lymphoma (PCNSL) in patients who are in complete remission after their initial treatment. In this trial, participants will either receive tirabrutinib or a placebo (a non-active pill) every day until their disease progresses or they experience side effects that are too severe. Patients will have regular check-ups at the clinic every four weeks to monitor their health and to get their medication.

To join this study, participants must be at least 18 years old and have been diagnosed with a specific type of B-cell lymphoma that is limited to the brain. They should have completed certain chemotherapy treatments and achieved a complete response, meaning no signs of cancer are detectable. Before enrolling, patients will go through a series of tests to ensure they are healthy enough to participate. Overall, this trial aims to find out if tirabrutinib can improve the length of time patients remain cancer-free compared to standard observation.

Gender

ALL

Eligibility criteria

• 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.