Title
Clarithromycin, Sulfamethoxazole/Trimethoprim or Observation in Newly Diagnosed Multiple Myeloma
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
Phase
Phase 2Lead Sponsor
Aalborg UniversityStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Multiple Myeloma InfectionIntervention/Treatment
sulfamethoxazole clarithromycin trimethoprim ...Study Participants
300This 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.
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
The choice of myeloma standard treatment is at the discretion of the treating investigator guided by the national Danish guidelines for treatment of multiple myeloma
P.o. clarithromycin 250 mg twice daily
P.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily
Observation without prophylactic antibiotic
p.o. clarithromycin 250 mg twice daily for 180 days
p.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days
Observation without prophylactic antibiotic treatment
Inclusion Criteria: 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 Exclusion Criteria: 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
