Clarithromycin, Sulfamethoxazole/Trimethoprim or Observation in Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Multiple Myeloma, Infection

Intervention / Treatment
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* Drug: Standard myeloma treatment
* Drug: Clarithromycin
* Drug: Sulfamethoxazole/trimethoprim
* Drug: Observation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clarithromycin<br>p.o. clarithromycin 250 mg twice daily for 180 days | Drug: Standard myeloma treatment<br>* 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<br>Drug: Clarithromycin<br>* P.o. clarithromycin 250 mg twice daily<br>|
| Experimental: Sulfamethoxazole/trimethoprim<br>p.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days | Drug: Standard myeloma treatment<br>* 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<br>Drug: Sulfamethoxazole/trimethoprim<br>* P.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily<br>|
| Experimental: Observation<br>Observation without prophylactic antibiotic treatment | Drug: Standard myeloma treatment<br>* 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<br>Drug: Observation<br>* Observation without prophylactic antibiotic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Infection, Clarithromycin, Trimethoprim-Sulfamethoxazole Combination