Studio Osservazionale Retrospettivo Multicentrico Sull'Utilizzo di Ibrutinib in Monoterapia o in Associazione a Immunochemioterapia Secondo Schema R-CHOP in Pazienti Adulti Con Diagnosi di PCNSL Ricaduto o Refrattario
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- To evaluate the efficacy in terms of overall rate of responses in patients treatment
研究概览
简要总结
PCNSL is a rare and aggressive subtype of B lymphoma that has been recognized as a distinct disease entity in the latest edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissue and is defined as DLBCL that develops exclusively in the brain parenchyma, spinal cord, leptomeninges and eye. In patients under 70 years of age without severe comorbidities, first-line treatment with induction chemo-immunotherapy according to the MATRix scheme (Methotrexate, Cytarabine, Tiothepa, Rituximab) and subsequent consolidation with HDCT followed by ASCT achieved the best results in terms of PFS and OS. Data on patients enrolled in a randomized phase 2 study showed an OS of 70% at a median FU of 88 months. In patients> 70 years of age or with low KPS, the prognosis remains significantly lower in the younger population. Several population studies have shown a stable increase over the past 30 years in terms of PFS and OS in patients aged under 70 years, while in patients over 70 years or with KPS <70%, the survival curves are not satisfactory. in part because these patients are often referred to BSC alone, despite the benefit in PFS and OS demonstrated with HD-MTX-based treatments (≥1 g / m2) combined with oral alkylating agents or cytarabine in high doses.
详细描述
Historically, HDCT followed by ASCT has not been considered a feasible option for elderly patients, although recent data collected in the "real life" setting and a pilot study conducted in Germany demonstrate that maintenance of the dose intensity of HD-MTX and treatment completion with HDCT / ASCT-based consolidation are similar to those in clinical studies. However, 20 to 50% of newly diagnosed PCNSL patients do not achieve a complete response with currently available treatment regimens, highlighting the need for improved induction strategies. Furthermore, even after a complete response, patients with PCNSL may experience relapse, especially in the elderly. First-line treatment failure usually occurs (70-75% of cases) within the first two years and the prognosis of this population is extremely poor as demonstrated in a retrospective study of more than 250 patients with PCNSL R / R who reported median PFS and OS at first relapse / progression of 2.2 and 3.5 months, respectively. Similar results have also been highlighted in several prospective studies in which the PFS and OS curves are equivalent. There is currently no standard of treatment for the treatment of patients with PCNSL R/R. Data extrapolated from the long-term FU of a randomized phase 2 trial suggests that patients with relapses more than 36 months after the end of first-line methotrexate-based immuno-chemotherapy could benefit from a rechallenge with the same treatment. On the other hand, for patients refractory or with relapses within 36 months or not eligible for HD-MTX, the best therapeutic choice is represented by enrollment in a clinical trial. In the absence of this option, the therapeutic choice is based on the experience of phase 2 studies.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological diagnosis of DLBCL
- •Disease localized exclusively in the CNS (brain, meninges, cranial nerves, eyes and / or spinal cord) both at first diagnosis and at failure
- •Progressive or recurrent disease
- •Previous treatment with high-dose methotrexate-based chemotherapy ± WBRT
- •Age 18 - 80 years
- •ECOG performance status 0-3
- •Adequate hematopoiesis (platelets> 25,000 / mm3, hemoglobin> 8 g / dL, ANC> 1,000 / mm3), renal (serum creatinine <2 times UNL and creatinine clearance ≥40 mL / min), cardiac (VEF ≥50% ) and liver function (SGOT / SGPT <3 times UNL, bilirubin and alkaline phosphatase <2 times UNL).
- •Patients who have been given treatment with ibrutinib, alone or in combination with immunochemotherapy, and who have or have not received the same.
排除标准
- •Patients with concomitant extra-CNS disease at presentation or relapse
- •Symptomatic coronary heart disease, cardiac arrhythmias not well controlled with drugs, or myocardial infarction within the past 6 months (New York Heart Association class III or IV heart disease)
- •Any other serious medical condition that could compromise the patient's ability to adhere to treatment.
- •Presence of any psychological, family, sociological or geographical condition that may hinder compliance with the study protocol and the follow-up program.
- •In therapy with strong CYP3A inhibitors
研究组 & 干预措施
Patients diagnosed with r/r PCNSL
Adult patients diagnosed with relapsed or refractory PCNSL who in the period between August 2020 and May 2022 were candidates for treatment with ibrutinib alone or in combination with R-CHOP or R-CHOP like (in compassionate use, or off- label).
干预措施: Ibrutinib (Drug)
结局指标
主要结局
To evaluate the efficacy in terms of overall rate of responses in patients treatment
时间窗: 6MONTH
To evaluate the efficacy in terms of overall rate of responses to treatment (ORR = sum of complete responses \[CR\] + partial responses \[PR\]) according to the IPCG 2005 criteria in a retrospective cohort of patients with relapsed / refractory PCNSL undergoing treatment with ibrutinib given as monotherapy or in combination with R-CHOP immuno-chemotherapy.
次要结局
- Evaluate the effectiveness in terms of overall survival (OS);(6MONTH)
- Verification of the safety of the ibrutinib monotherapy and in combination with R-CHOP(6MONTH)
- To evaluate the role of consolidation therapy with high-dose chemotherapy(6MONTH)
- Frequency of invasive fungal infections after prophylactic antifungal therapy(6MONTH)
- Evaluate the effectiveness in terms of progression-free survival (PFS);(6MONTH)
研究者
Andrés José Maria Ferreri
LYMPHOMA UNIT DIRECTOR
IRCCS San Raffaele