A Phase 2 Study of Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary Central Nervous System Lymphoma
概览
- 阶段
- 2 期
- 干预措施
- Rituximab (where available)
- 疾病 / 适应症
- Non-hodgkin Lymphoma
- 发起方
- Canadian Cancer Trials Group
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- One year progression-free survival (PFS)
- 状态
- 招募中
- 最后更新
- 18天前
概览
简要总结
This study is being done to answer the following question: Can the addition of a new drug to the usual treatment lower the chance of primary central nervous system lymphoma growing or spreading?
This study is being done to find out if this approach is better or worse than the usual approach for this type of cancer. The usual approach is defined as the care most people get for Primary Central Nervous System Lymphoma (PCNSL).
详细描述
If a patient decides to take part in this study, the patient will get 3 months of treatment with methotrexate and ibrutinib as well as rituximab (if rituximab is given for PCNSL in the applicable province). This will be followed by treatment with ibrutinib alone for up to 2 years of total treatment time. After finishing study treatment, and even if patients stop treatment early, the study doctor will continue to follow the patient's condition for the rest of their life or until all study results are known (in approximately 6 years), watch for side effects and keep track of the patient's health. If there are any side effects that may be related to ibrutinib, the patient will be asked to come back to the clinic every 3 months until side effects improve. If there are no side effects from ibrutinib the patient will be asked to come back to clinic every 6 months until cancer worsens, and then every 6 months may be contacted by phone.
研究者
入排标准
入选标准
- •Patients must have histological or cytological evidence of primary central nervous system (CNS) lymphoma (PCNSL); patients with vitreo-retinal lymphoma (NHL) or cerebrospinal fluid (CSF) positive disease are eligible providing there is CNS involvement on MRI compatible with PCNSL
- •Patients must be 18 years of age or older
- •Patients must be ineligible (≥65 years old or comorbidities) for high-dose chemotherapy and autologous stem cell transplantation. Patients must be considered fit, as determined by the treating physician, to receive high dose methotrexate, ibrutinib and rituximab as per protocol
- •Patients must have consented to the release of a tumour block from their brain tumour, if available (see Section 12.0). The centre/pathologist must have agreed to the submission of the specimen(s).
- •Presence of radiological documented disease. Patients believed to have residual disease following a complete resection, even if radiology is negative or equivocal, are eligible provided they are planned for standard of care methotrexate/rituximab.
- •No prior systemic therapy other than the following situations:
- •Methotrexate +/- rituximab: Patients may have received one cycle of methotrexate with or without rituximab as standard of care therapy, but must be enrolled no longer than 4 weeks after first dose of methotrexate corticosteroids for PCNSL is permitted.
- •Use of corticosteroids (topical are permitted) on study (except for short-term treatment of infusion reactions and nausea prophylaxis) is not permitted. Patients receiving corticosteroids me be eligible, providing:
- •they are receiving not more than dexamethasone 8mg/day (or equivalent)
- •The corticosteroid will be tapered and completely discontinued within 7 days of starting the study protocol treatment. Patients who would require continued or concurrent treatment with systemic steroids are not eligible.
排除标准
- •Patients with secondary central nervous system non-Hodgkin lymphoma (NHL).
- •Patients with significant third space accumulation (pleural effusions, ascites) which cannot be adequately drained in advance of methotrexate administration
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. However, patients on active anticancer therapy for other advanced or metastatic malignancies are not eligible.
- •Patients with a known hypersensitivity to the study drugs or their components
- •Active, uncontrolled bacterial, fungal, or viral infection within 7 days prior to enrollment. Patients with hepatitis B serology suggestive of past infection (for example anti-HB-c positive but HBsAG and anti-HBs negative) are eligible if they are HBV DNA negative are being or will be concurrently treated with anti-viral therapy. Patients with a history of hepatitis C which has been treated and is no longer active are eligible. Patients with known human immunodeficiency virus (HIV) with CD4 count \< 350 cells/microliter are ineligible. Patients who are HIV positive are eligible, provided:
- •They have received antiretroviral therapy for at least 4 weeks prior to enrollment, and the anti-viral drugs used are not known to have clinically relevant drug-drug interactions with ibrutinib AND
- •HIV viral load must be \< 400 copies/ml within 16 weeks prior to enrollment AND No history of opportunistic infections within the past year
- •Serious illnesses or medical conditions which would not permit the patient to be managed according to protocol
- •Patients may not receive concurrent treatment with other anti-cancer therapy or investigational agents while on protocol therapy
- •Patients with prior allogenic bone marrow transplant or double umbilical cord blood transplantation.
研究组 & 干预措施
Methotrexate, Ibrutinib +/- Rituximab
Cycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally
干预措施: Rituximab (where available)
Methotrexate, Ibrutinib +/- Rituximab
Cycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally
干预措施: Methotrexate
Methotrexate, Ibrutinib +/- Rituximab
Cycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally
干预措施: Ibrutinib
结局指标
主要结局
One year progression-free survival (PFS)
时间窗: 5 years
次要结局
- Overall Response Rate (ORR = CR+CRu+PR) and complete response (CR) rate(5 years)
- 2-year progression-free survival(5 years)
- Overall survival (OS)(5 years)
- 1-year event-free survival (EFS)(5 years)
- To determine the impact on cognitive functioning of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-Cog(5 years)
- Number and severity of adverse events(5 years)
- To determine the impact on health-related quality of life of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-BR(5 years)