NCT06940791招募中2 期
Tirabrutinib Maintenance Versus Placebo in Patients With Primary Central Nervous System Lymphoma in Complete Remission: a Randomized Phase II Study (JCOG2104)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS) based on independent review committee (IRC) assessment
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathological diagnosis of B cell lymphoma.
- •Newly-diagnosed PCNSL confined to the cerebrum, cerebellum and brainstem. Patients with or without interocular lymphoma are eligible.
- •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.
- •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.
- •Patients with a single lesion, or multiple lesions, are eligible.
- •Patients 18 years old or older at the time of registration.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1,
- •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
- •Complete response (CR) or complete response unconfirmed (CRu) based on the International PCNSL Collaborative Group (IPCG) criteria.
- •Within 60 days from the last dose of induction or consolidation chemotherapy.
- •No treatment history of radiotherapy for PCNSL.
- •Refused to receive consolidation radiotherapy.
- •No treatment history of chemotherapy or radiotherapy, except for stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) for non-cancer diseases (such as arteriovenous malformations).
- •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
- •Written informed consent.
排除标准
- •Synchronous or metachronous malignancies.
- •Infections requiring systemic treatment at the time of registration.
- •Body temperature >=38 degree celsius at the time of registration.
- •Serious lung disorders, such as interstitial pneumonia, obstructive lung disease, hypersensitive pneumonitis, symptomatic bronchospasm) at the time of registration.
- •History or presence of aspergillus pneumonitis or pneumocystis pneumonia.
- •History of serious drug allergy or serious anaphylaxis.
- •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.
- •Treated by anticoagulants at the time of registration.
- •Treated by antiplatelets at the time of registration.
- •Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
- •Immune deficiency, such as acquired immunodeficiency syndrome (AIDS), X-linked agammaglobulinemia, chronic granulomatous disease, Wiskott-Aldrich syndrome, or any other iatrogenic immunosuppressive conditions.
- •Post organ transplant immunosuppression.
- •Prednisone use of >10 mg/day for condition other than intracranial tumor, or regular use of immunosuppressants.
- •Uncontrolled diabetes mellitus.
- •Treated either by CYP3A4 inhibitors, CYP3A4 inducers, or P-gp inducers within 14 days prior to registration.
- •Gadolinium allergy.
- •Positive HIV antibody.
- •Positive HBs antigen.
- •Positive HBs antibody or HBc antibody, and HBV-DNA positive.
- •Positive HCV antibody.
- •Unable to take oral medicine,
- •Females during pregnancy, or within 28 days postpartum, or during lactation. Males who wish childbearing of his partner.
- •Prior history of treatment by BTK inhibitors.
- •Severe psychiatric disorders.
研究组 & 干预措施
Standard arm
Placebo Comparator
Observation with placebo
干预措施: Placebo (Drug)
Experimental arm
Experimental
Tirabrutinib maintenance therapy
干预措施: Tirabrutinib (Drug)
结局指标
主要结局
Progression-free survival (PFS) based on independent review committee (IRC) assessment
时间窗: From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months
次要结局
- Progression-free survival (PFS) determined by investigator(From the date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 78 months)
- Overall survival (OS)(From the date of registration until the date of death from any cause, assessed up to 78 months)
- PFS/OS in the maintenance per protocol group(PFS: From the date of registration until the date of first progression or date of death from any cause, whichever came first, assessed up to 78 months. OS: From the date of registration until the date of death from any cause, assessed up to 78 months.)
- PFS/OS by the induction therapy regimen with or without consolidation therapy(PFS: From the date of registration until the date of first progression or date of death from any cause, whichever came first, assessed up to 78 months. OS: From the date of registration until the date of death from any cause, assessed up to 78 months.)
- Proportion of patients without deterioration in health-related QOL(Among patients eligible for HR-QOL assessment, the proportion without deterioration at the following time points: pre-treatment baseline (after registration but before initiation of the study treatment), 48 weeks, 2 years, and 3 year)
- Incidence rate of adverse events(During the intervention up to 78 months, or for those who discontinued the intervention, assessed until 30 days after the last date of intervention or the date of initiation of post-study therapy, whichever came first, assessed up to 78 months.)
- Proportion of patients without neurological cognitive function (NCF) deterioration(Among patients eligible for NCF assessment, the proportion without deterioration in each assessment item at the following time points: pre-treatment baseline (after registration but before initiation of the study treatment), 48 weeks, 2 years, and 3 year)
研究者
Motoo Nagane
Professor, Department of Neurosurgery
Kyorin University
研究点 (1)
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