A Open Label, Phase II, Non Randomized, Clinical Trial of Chemotherapy Treatment With 5-Azacytidine Plus Valproic Acid and Eventually Atra for Patients Diagnosed With Intermediate II and High Risk Myelodysplastic Syndrome (MDS). EudraCT Number 2005-004811-31. GIMEMA Protocol MDS0205
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 7
- 主要终点
- The Primary Objective of the Trial is to Assess the Efficacy of the Combined Use of Valproic Acid (VPA) in Combination With 5-Azacytidine (5-Aza C) in the Treatment of MDS.
研究概览
简要总结
The primary objective of the trial is to assess the activity of the combined use of Valproic Acid (VPA)in combination with 5-Azacytidine (5-Aza C) in the treatment of MDS.
Activity will be evaluated as percentage of patients achieving complete or partial remission.
详细描述
Myelodisplastic Syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis (as a result of increased apoptosis of precursor cells), progressive peripheral cytopenia, with a tendency to evolve to acute leukemia.
The term "syndrome" represents the wide clinical spectrum of this group of diseases, ranging from mild and stable cytopenia, with a low risk of leukemic conversion and a life expectancy of several years, to true pre-leukemia.
The International MDS Risk Analysis Workshop recently developed a consensus risk-based International Prognostic Score System (IPSS) for primary MDS, which has markedly improved prognostic stratification of MDS patients. Following IPSS,it is now possible to identify patients (i.e. Hig-Risk and Intermediate-2-Risk patients) with a bad prognosis (i.e. a life-expectancy < 1 year) due to a high risk of leukemic evolution.
Currently, allogeneic stem cell transplantation represents the only curative therapy for this subgroup of high-risk patients. However, this therapeutic option is often precluded for several reasons (old age, comorbidity, lack of suitable donor).
Among the experimental treatments hitherto tested, 5-Azacitidine (5-Aza) has recently shown promising results. Moreover, the biological experimental data suggest that the association of 5-Aza with histone deacetylase inhibitors, such as Valproic Acid, and with differentiating agents, such as retinoic acid, might be synergistic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Have a diagnosis of refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-t) according to the French-American-British classification system for MDS with an International Prognostic Scoring System score of INT-2 or High or diagnosis of Myelodysplastic CMMoL per a modified FAB criteria and a relatively high risk of AML transformation;
- •Age ≥18 years;
- •life expectancy ≥3 months;
- •Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission;
- •Signed written informed consent according to IGH/EU/GCP and national local laws;
- •Eastern Cooperative Oncology Group Performance Status Grade of 0-2 (Appendix D);
- •Serum bilirubin levels ≤1.5 x the upper limit of the normal (ULN) range for the laboratory; higher levels are acceptable if these can be attributed to active hemolysis (as indicated by positive direct Coombs' testing, decreased haptoglobin level, elevated indirect bilirubin and/or lactate dehydrogenase), or ineffective erythropoiesis (as indicated by bone marrow findings);
- •Serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels ≤2 x ULN;
- •Women of childbearing potential may participate, providing they meet the following conditions:
- •Must not start a pregnancy throughout the study and for 6 months following the date of the last dose of study medications;
- •Must have a negative serum pregnancy test obtained within 48 hours prior to Day
- •Males with female partner of childbearing potential must avoid fathering throughout the study and for 6 months following the date of the last dose of study medication.
- •Exclusion criteria:
- •acute myeloid leukaemia (i.e. bone marrow blasts >30%);
- •concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma);
- •severe renal impairment (creatinine clearance <30 ml/min);
- •pregnant or lactating, or are potentially fertile (both males and females) and have not agreed to avoid pregnancy during the trial period;
- •they have liver disease characterized by AST and ALT level >2X ULN and total bilirubin > 1.5X ULN (unless due to active hemolysis or ineffective erythropoiesis;
- •HIV infection;
- •active, uncontrolled HCV or HBV infections or liver cirrhosis;
- •clinically relevant neurological diseases;
- •psychiatric illness that would prevent granting of informed consent;
- •hypersensitivity (known or suspected) to Azacytidine or Mannitol
- •prior Treatments: Prior investigational drugs (within 30 days) Radiation therapy, chemotherapy, or cytotoxic therapy for non- MDS conditions within the previous 6 months Growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days Androgenic hormones during the previous 14 days Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS.
排除标准
- 未提供
结局指标
主要结局
The Primary Objective of the Trial is to Assess the Efficacy of the Combined Use of Valproic Acid (VPA) in Combination With 5-Azacytidine (5-Aza C) in the Treatment of MDS.
时间窗: At 60 months
Overall survival
次要结局
- Time to Transformation to AML(At 60 months)