Clinical trial NCT02624440: Clarithromycin, Sulfamethoxazole/Trimethoprim or Observation in Newly Diagnosed Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma
Infection
Keywords: Multiple Myeloma
Infection
Clarithromycin
Trimethoprim-Sulfamethoxazole Combination
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Danish Myeloma Study Group
First posted: 2015-12-08
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic
timeFrame: One year
Secondary outcomes:
measure: Response rates in the group of patients treated with clarithromycin compared to the other patients in the study
timeFrame: One year
measure: Comparison of adverse events assessed by CTCAE v4.0 in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic
timeFrame: 6 months
measure: Comparison of overall survival between patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic
timeFrame: Three years
measure: Quality of life assessed by EORTC QLQ-MY20
timeFrame: One year
measure: Quality of life assessed by EORTC QLQ-C30
timeFrame: One year
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Hematology, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Hematology, Rigshospitalet
city: Esbjerg
country: Denmark
facility: Department of Hematology, Esbjerg Sygehus
city: Herlev
country: Denmark
facility: Department of Hematology, Herlev Hospital
city: Holstebro
country: Denmark
facility: Department of Hematology, Hospitalsenheden Vest
city: Odense
country: Denmark
facility: Department of Hematology, Odense University Hospital
city: Roskilde
country: Denmark
facility: Department of Hematology, Roskilde Hospital
Study officials:
affiliation: Aalborg University Hospital
name: Henrik Gregersen, MD
role: PRINCIPAL_INVESTIGATOR
References: