A Phase II Study of Azacitidine (Vidaza®) Combined to Epoetin Beta (NeoRecormon®) in IPSS Low-risk and Intermediate-1 MDS Patients, Resistant to ESA
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 29
- 主要终点
- To determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria
研究概览
简要总结
The study is aimed to treat low-risk MDS patients,who are dependent on red-blood cell transfusion due to disease-related anemia, and who have a proven resistance towards treatment with erythropoetin-stimulating agents (ESA). The study randomizes patients to receive a treatment with the demethylating agent 5-azacytidine alone or in combination with an ESA. The study thus evaluates, if efficacy of 5-azacytidine, notably on the red-blood cell transfusion-dependence is comparable/inferior to a combination treatment with azacitidine and an ESA (that is if 5-azacytidine can overcome the resistance towards ESA). Being a phase II study, the study assesses, duration of erythroid response, overall survival and time to progression as well as toxicity.
详细描述
Phase II Study of Azacitidine (Vidaza®) Combined to Epoetin Beta (NeoRecormon®) in IPSS Low-risk and Intermediate-1 MDS Patients, Resistant to ESA
The Primary Endpoint of this study is to determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria.
The Secondary Endpoints are to determine the percentage of major HI-E and minor HI-E after 4 and 6 courses according to IWG 2000, the HI-E IWG 2006 criteria, the duration of erythroid response, the red blood cell transfusion independence at 4 and 6 months, the overall survival and time to IPSS progression and the toxicity (NCI-CTAE).
The trial will enroll 98 patients (49 patients per arm)
Treatment in arm A:
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
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
- •MDS defined as
- •RCMD, RA with or without ring sideroblasts
- •RAEB 1, or CMML 1, if WBC < 13 G /l according to the WHO classification
- •with a low or int-1 IPSS score AND
- •primary or secondary resistance to epoetin alpha/ beta (> 60000 U/w) or darbepoetin (> 250ug/w), administered for at least 12 weeks
- •requirement of RBC transfusions > 4 U in the previous 8 weeks
- •Aged 18 years or more
- •Adequate contraception, if relevant
- •Negative pregnancy test if relevant
- •Written Informed consent
- •Ability to participate to a clinical trial and adhere to study procedures
- •Health insurance
排除标准
- •Therapy-related MDS (after chemo- or radiotherapy for a previous neoplasm or immune disorder)
- •Patients with a planned allogeneic bone marrow transplantation
- •Creatininemia >1.5 upper normal value or estimated Ccr less than 30ml/mn
- •ALAT and ASAT >2.5 upper normal value
- •Bilirubin >2N, except unconjugated hyperbilirubinemia due to MDS-related dyserythropoiesis
- •Heart failure NYHA > II
- •Known allergy to mannitol
- •Other tumor, unstable for the last three years, except in situ uterine carcinoma or basal skin tumor
- •ECOG > 2
- •Life expectancy less than 3 months
研究组 & 干预措施
Arm A
Azacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses and 12 additional maintenance courses in responders.
干预措施: Azacitidine (Drug)
Arm B
Azacitidine: 75mg/sqm SQ per day for 5 days every 28 days for 6 courses AND
Epoetin beta : 60000U weekly SQ injections (to be adapted according to Hb as described above)
12 additional maintenance courses are planned in responders
干预措施: Azacitidine (Drug)
Arm B
Azacitidine: 75mg/sqm SQ per day for 5 days every 28 days for 6 courses AND
Epoetin beta : 60000U weekly SQ injections (to be adapted according to Hb as described above)
12 additional maintenance courses are planned in responders
干预措施: Epoetin beta (Drug)
结局指标
主要结局
To determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria
时间窗: after 6 courses of treatment in the respective treatment arm
次要结局
- Degree and duration of erythroid response (including red blood cell transfusion independence),overall survival and time to progression and toxicity(after 4 and 6 months of treatment until the end of study)