Observational Study on Eltrombopag in Hypocellular Myelodysplastic Neoplasms
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 26
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Hypocellular myelodysplastic neoplasms (h-MDS) are a distinct entity introduced in the 2022 WHO classification. They are characterized by reduced bone marrow cellularity and may share several clinical, morphological, immunological, and molecular features with aplastic anemia (AA), making the differential diagnosis between the two conditions challenging.
Eltrombopag, a thrombopoietin receptor agonist, has demonstrated efficacy in patients with severe AA and has also shown activity in lower-risk MDS, with bone marrow hypocellularity identified as a potential predictor of response. In Italy, eltrombopag has been used off-label in patients with h-MDS and clinically relevant cytopenias. However, systematic real-world data on its effectiveness and safety in this patient population, either as monotherapy or in combination with immunosuppressive therapy (IST), remain limited.
This is an observational study. We plan to analyse all patients with h-MDS consecutively diagnosed and included in the FISIM registry in 26 Italian centres.
Study duration: 12 months Data to be collected: demographic, disease characteristics at diagnosis (blood count, morphology, histopathology, cytogenetics, multiparameter flow cytometry, presence of PNH clone, molecular data), response to treatment according to IWG criteria, progression to AML rate and survival.
Centralized revision of bone marrow biopsy: bone marrow biopsy at diagnosis will be centrally reviewed
详细描述
Myelodyspastic neoplasms (MDS) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis, morphological dysplasia and a variable risk of transformation into acute myeloid leukaemia (AML). These diseases generally occur in the elderly, with a median age of onset above 70 years.
Recently, major advances in molecular technology and the development of next-generation sequencing (NGS) have deepened our understanding of MDS pathobiology. Hence, the International Consensus Classification (ICC), and the World Health Organization (WHO) proposed in 2022 a revision to the current classification system.
Hypocellular MDS (h-MDS), defined as a bone marrow cellularity of less than 30% in individuals younger than 60 years of age or less than 20% in those older than 70 years, is a new entity included in the WHO-2022 classification but not present in the ICC, accounting for 10-27% of all MDS cases (2,5-7).
The different prevalences of h-MDS are reported because derive from heterogeneity across the studies in the criteria used to define bone marrow hypocellularity, or the inclusion of de novo or both de novo and secondary cases, or differences in genetic and environmental backgrounds among the populations studied and in the possible contamination with patients with aplastic anaemia (AA). Hypocellular MDS are characterized by bone marrow hypoplasia, a low rate of progression to acute myeloid leukemia (AML), and poor response to conventional MDS therapies. For at least some types of AA and MDS, the overwhelming body of evidence points to a shared pathogenesis and, more speculatively, a shared etiology.
The pathogenesis of h-MDS involves immune system activation against hemopoietic precursor, which may explain the favourable response to immunosuppressive therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
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
- •Adult patients (i.e. aged ≥18 years) diagnosed with MDS-h according to WHO 2022
- •IPSS-R risk very-low to intermediate
- •De novo or therapy related MDS
- •Availability of bone marrow sample for central revision
- •Treatment with eltrombopag, in monotherapy or associated with IST, as first -line therapy or as a subsequent therapy to the first line
排除标准
- •Unavailability of bone marrow sample for central revision
研究组 & 干预措施
Adult patients diagnosed with h-MDS according to WHO 2022 and treated with eltrombopag
Adult patients diagnosed with h-MDS according to WHO 2022 and treated with eltrombopag included in FISiM registry
- IPSS-R very-low to intermediate
- De novo or therapy related Available bone marrow sample for central revision
干预措施: Eltrombopag (ELT) (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From initiation of eltrombopag treatment through the last available response assessment, up to study completion.
Overall response rate to eltrombopag according to the International Working Group (IWG) response criteria (Cheson 2006)
次要结局
- Overall Response Rate (ORR) of eltrombopag combined with immunosuppressive drugs(From initiation of eltrombopag treatment through the last available response assessment, up to study completion.)
- Overall Survival (OS)(From diagnosis and from initiation of eltrombopag treatment until death or last available follow-up, up to study completion.)
- Duration of Response (DoR)(From achievement of response until loss of response, death, or last available follow-up, up to study completion.)
- Adverse Events (AE) and Serious Adverse Events (SAE)(From initiation of eltrombopag treatment through the end of treatment, up to study completion.)
- Acute Myeloid Leukemia (AML) Rate(From diagnosis through study completion.)
- Time to AML Progression(From diagnosis and from initiation of eltrombopag treatment until AML progression or last available follow-up, up to study completion.)