A Randomized, Open-label Phase III Study of Clarithromycin, Sulfamethoxazole/Trimethoprim or Observation in Combination With Standard Therapy in Patients With Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 2 期
- 入组人数
- 300
- 试验地点
- 8
- 主要终点
- Comparison of frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic
研究概览
简要总结
This study evaluates the effect of prophylactic antibiotics in multiple myeloma. One third of patients will received treatment with clarithromycin, one third of patients will receive treatment with sulfamethoxazole/trimethoprim and one third will be observed without prophylactic antibiotics. All patients receive concurrent anti-myeloma treatment.
详细描述
There is a need for improvement of the prognosis in elderly myeloma patients. The patients are fragile due to age and severe comorbidity. Infections are frequent during the course of initial myeloma treatment and contribute to the high morbidity and mortality in elderly patients. Furthermore infections often lead to delay in myeloma treatment and to dose reduction. The use of primary antibiotic prophylaxis might influence the frequency of these complications. In the study myeloma patients who are ineligible for high-dose melphalan with stem cell support are randomised to either p.o. clarithromycin 250 mg twice daily for 180 days, p.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days or observation without prophylactic antibiotics. All patients receive concurrent myeloma treatment at the discretion of the treating physician. The choice of anti-myeloma treatment has to be settled before randomization. The study evaluates the frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observation
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
- •Myeloma diagnosis according to IMWG criteria
- •Treatment demanding disease
- •Signed informed consent given prior to any study related activities, except bone marrow samples for diagnosis, FISH, biobanking, and skeletal x-ray
- •Age > 18 years
排除标准
- •Allogeneic transplantation scheduled as a part of the treatment
- •High-dose melphalan with stem cell support scheduled as a part of the treatment
- •Myeloma treatment prior to entry in the study, except radiotherapy, bisphosphonates/denusumab or corticosteroids for symptom control
- •Concurrent disease making clarithromycin or sulfamethoxazole/trimethoprim treatment unsuitable
- •Positive pregnancy test (only applicable for women with childbearing potential)
- •Known or suspected hypersensitivity or intolerance to claritromycin, sulfamethoxazole or trimethoprim
- •Prolonged QT corrected (QTc) interval ( > 500 msec on screening ECG)
- •Concurrent treatment with cabergoline, fluconazole, ketoconazole, pimozide, quetiapine, sirolimus, verapamil, tacrolimus, ergot alkaloid or methotrexate
- •Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, uncontrolled angina or known cardiac amyloidosis
- •Severe renal dysfunction (estimated creatinine clearance <10 mL/min)
- •Serious medical or psychiatric illness which, in the judgment of the investigator, would make the patient inappropriate for entry into the study
研究组 & 干预措施
Clarithromycin
p.o. clarithromycin 250 mg twice daily for 180 days
干预措施: Clarithromycin (Drug)
Clarithromycin
p.o. clarithromycin 250 mg twice daily for 180 days
干预措施: Standard myeloma treatment (Drug)
Sulfamethoxazole/trimethoprim
p.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days
干预措施: Standard myeloma treatment (Drug)
Sulfamethoxazole/trimethoprim
p.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days
干预措施: Sulfamethoxazole/trimethoprim (Drug)
Observation
Observation without prophylactic antibiotic treatment
干预措施: Standard myeloma treatment (Drug)
Observation
Observation without prophylactic antibiotic treatment
干预措施: Observation (Drug)
结局指标
主要结局
Comparison of frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic
时间窗: One year
次要结局
- Response rates in the group of patients treated with clarithromycin compared to the other patients in the study(One year)
- Comparison of adverse events assessed by CTCAE v4.0 in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic(6 months)
- Comparison of overall survival between patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic(Three years)
- Quality of life assessed by EORTC QLQ-MY20(One year)
- Quality of life assessed by EORTC QLQ-C30(One year)
研究者
Henrik Gregersen
Consultant
Aalborg University Hospital