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

Phase 2
Conditions
Multiple Myeloma
Infection
Interventions
Drug: Standard myeloma treatment
Drug: Observation
Registration Number
NCT02624440
Lead Sponsor
Henrik Gregersen
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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ClarithromycinStandard myeloma treatmentp.o. clarithromycin 250 mg twice daily for 180 days
ClarithromycinClarithromycinp.o. clarithromycin 250 mg twice daily for 180 days
Sulfamethoxazole/trimethoprimStandard myeloma treatmentp.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days
Sulfamethoxazole/trimethoprimSulfamethoxazole/trimethoprimp.o. sulfamethoxazole/trimethoprim 400/80 mg twice daily for 180 days
ObservationStandard myeloma treatmentObservation without prophylactic antibiotic treatment
ObservationObservationObservation without prophylactic antibiotic treatment
Primary Outcome Measures
NameTimeMethod
Comparison of frequency of infections in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibioticOne year
Secondary Outcome Measures
NameTimeMethod
Response rates in the group of patients treated with clarithromycin compared to the other patients in the studyOne year
Comparison of adverse events assessed by CTCAE v4.0 in patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibiotic6 months
Comparison of overall survival between patients treated with clarithromycin, sulfamethoxazole/trimethoprim or observed without prophylactic antibioticThree years
Quality of life assessed by EORTC QLQ-MY20One year
Quality of life assessed by EORTC QLQ-C30One year

Trial Locations

Locations (8)

Department of Hematology, Aalborg University Hospital

🇩🇰

Aalborg, Denmark

Department of Hematology, Rigshospitalet

🇩🇰

Copenhagen, Denmark

Department of Hematology, Esbjerg Sygehus

🇩🇰

Esbjerg, Denmark

Department of Hematology, Hospitalsenheden Vest

🇩🇰

Holstebro, Denmark

Department of Hematology, Roskilde Hospital

🇩🇰

Roskilde, Denmark

Department of Hematology, Aarhus University Hospital

🇩🇰

Aarhus, Denmark

Department of Hematology, Odense University Hospital

🇩🇰

Odense, Denmark

Department of Hematology, Herlev Hospital

🇩🇰

Herlev, Denmark

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