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

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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06940791
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Kyorin University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	Japan
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Primary Central Nervous System Lymphoma

Arms & Interventions

Arms

Placebo Comparator: Standard arm

Observation with placebo

Experimental: Experimental arm

Tirabrutinib maintenance therapy

Interventions

Drug: - Tirabrutinib

Tirabrutinib (480 mg) taken orally daily at fasting condition

Drug: - Placebo

Placebo taken orally daily at fasting condition

Contact a Trial Team

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