Optimizing MATRix as Remission Induction in PCNSL: De-escalated Induction Treatment in Newly Diagnosed Primary CNS Lymphoma - a Randomized Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 331
- 试验地点
- 1
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival.
详细描述
This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival. Two arms are compared, in the experimental treatment group, participants receive one course of R/HD-MTX, followed by two courses of MATRix and autologous stem cell transplantation. In the control treatment, participants receive four coourses of MATRix followed by autologous stem cell transplantation.
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
- None (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
- •Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤
- •Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
- •Disease exclusively located in the CNS.
- •At least one measurable lesion.
- •Previously untreated patients (previous or ongoing steroid treatment admitted)
- •Negative pregnancy test
- •Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
- •Ability to understand the nature of the trial and the trial related procedures and to comply with them.
排除标准
- •Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
- •Systemic lymphoma manifestation (outside the CNS).
- •Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
- •Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years.
- •Previous Non-Hodgkin lymphoma at any time.
- •Inadequate renal function (clearance < 60 ml/min).
- •Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
- •Active hepatitis B or C disease.
- •Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
- •Third space fluid accumulation > 500 ml.
- •Hypersensitivity to study treatment or any component of the formulation.
- •Taking any medications that are likely to cause interactions with the study medication
- •Known or persistent abuse of medication, drugs or alcohol.
- •Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
- •Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
- •Previous participation in this trial.
- •Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
- •Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Current or planned pregnancy, nursing period
- •For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.
研究组 & 干预措施
Control treatment (Arm A)
Patients receive four courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) as induction treatment. Response assessment with gadolinium-enhanced brain MRI (centrally reviewed) takes place after course two and four. Patient with at least PR proceed to 3rd course of MATRix after first response assessment and to HCT-ASCT (BCNU 400 mg/m2, Thiotepa 4 x 5 mg/kg; i.v.) after second response assessment. Collection of autologous stem cells is planed after the second course of MATRix.
干预措施: Control intervention: four courses of MATRix (Drug)
Experimental treatment (Arm B)
As induction treatment, patients receive one course of Rituximab/HD-Methotrexate (Rituximab 375 mg/m2, HD-Methotrexate 3.5 g/m2; i.v.). In the absence of clinical signs of progression, patients proceed to two courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) followed by a response assessment with gadolinium-enhanced brain MRI (centrally reviewed). Patients with at least PR will proceed to HCT-ASCT (BCNU 400 mg/m2, thiotepa 4 x 5 mg/kg; i.v.). Collection of autologous stem cells is planed after the first course of MATRix
干预措施: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix (Drug)
结局指标
主要结局
Event-free survival (EFS)
时间窗: up to 24 months after end of treatment
time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first
次要结局
- Remission rate after consolidation therapy(30 days after ASCT)
- Overall survival (OS)(up to 24 months after end of treatment)
- Remission rate prior to consolidation therapy(assesed at RA II (Arm B: day 18-20 of cycle 2, each cycle is 21 days. Arm A: day 18-20 of cycle 4, each cycle is 21 days))
- Quality of life (QOL), EORTC QLQ-C30,(up to 24 months after end of treatment)
- Progression free survival (PFS)(up to 24 months after end of treatment)
- rate of patients reaching consolidation therapy(determined up to 4 weeks after response assessment II)
- Quality of life (QOL), QLQ-BN20(up to 24 months after end of treatment)