Phase II Study of Bortezomib Dexamethasone and High-dose Melphalan in Patients With Relapse After High-dose Melphalan With Autologous Stem Cell Support
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 17
- 主要终点
- Comparison of the event free survival after first high-dose melphalan with stem cell support (ASCT) and a second ASCT combined with bortezomib treatment of first relapse
研究概览
简要总结
The prognosis after retreating with high-dose melphalan with stem cell support after first relapse after high-dose treatment is dependent on the time to first relapse. Bortezomib can increase chemosensitivity of e.g. melphalan. The trial aims at determining the toxicity of adding bortezomib to high-dose melphalan with stem cell support and evaluating whether the time to a second relapse can be prolonged.
详细描述
Patients with multiple myeloma who have their first treatment demanding relapse after an initial treatment with high-dose melphalan with autologous stem cell support and who have more than 2.0 x 10^6 CD34+ stem cells pr kg bodyweight in the freezer can be included in the trial.
After disease status with basic clinical biochemistry, M-protein in blood and urine, bone marrow investigation including immunophenotyping and total skeletal x-ray the patients are treated with three courses of standard bortezomib (1.3 mg/sqm Days 1,4,8,11) and dexamethasone 20 mg days 1,2,4,5,8,9,11,12. Within 4 weeks the patients receive bortezomib days -5 and -2, high-dose melphalan (200 mg/sqm) day -2, and subsequent at least 2.0 x 10^6 CD34+ stem cells pr kg body weight.
The first month after high-dose therapy the patients are followed closely for toxicity according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE), Version 3.0.
The patients are evaluated for response according to EBMT criteria and for event (death or progressive disease).
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
- •First relapse after ASCT
- •Symptomatic myeloma
- •More than 2,0 x 10^6 CD34+ stem cells / kg bodyweight in the freezer for stem cell support
- •Signed informed consent given prior to any study related activities have been performed
- •Age > 18 years
排除标准
- •Allogeneic transplantation scheduled as a part of the treatment
- •Expected survival of less than one month.
- •Performance status (WHO) > 3
- •Neuropathy > Grade 3 (neurological symptoms interfering with ADL)
- •Non-secreting myeloma
- •Other concurrent disease making bortezomib treatment unsuitable
- •Positive pregnancy test (only applicable for women with childbearing potential)
- •Has known or suspected hypersensitivity or intolerance to melphalan, dexamethasone, boron, mannitol, or heparin, if an indwelling catheter is used
- •Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 6, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
- •History of hypotension or has decreased blood pressure (sitting systolic blood pressure [SBP] <= 100 mmHg and/or sitting diastolic blood pressure [DBP] <= 60 mmHg)
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- •Have received an experimental drug or used an experimental medical device within 4 weeks prior to inclusion into the study
结局指标
主要结局
Comparison of the event free survival after first high-dose melphalan with stem cell support (ASCT) and a second ASCT combined with bortezomib treatment of first relapse
时间窗: 3 years
次要结局
- Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning(3 years)
- Response rate of the second ASCT(3 years)
- Marrow regeneration(3 years)
- OS compared with the OS of matched controls from the former NMSG(3 years)