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

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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma; Infection
• Intervention / Treatment: Drug: Standard myeloma treatment; Drug: Clarithromycin; Drug: Sulfamethoxazole/trimethoprim; Drug: Observation

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

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sanne Kjaer; Phone Number: +45 97663884; Email: smk@rn.dk
• Study Contact Backup: Name: Ulla Kjaer; Phone Number: +45 97663882; Email: u.kjaer@rn.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Department of Hematology, Aalborg University Hospital
    • Principal Investigator: Henrik Gregersen, MD
  • Aarhus, Denmark, 8000
    • Recruiting
    • Department of Hematology, Aarhus University Hospital
    • Principal Investigator: Niels Frost Andersen, MD
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Hematology, Rigshospitalet
    • Principal Investigator: Annette Juul Vangsted, MD
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Department of Hematology, Esbjerg Sygehus
    • Principal Investigator: Per Trøllund Pedersen
  • Herlev, Denmark, 2730
    • Recruiting
    • Department of Hematology, Herlev Hospital
    • Principal Investigator: Carsten Helleberg, MD
  • Holstebro, Denmark, 7500
    • Recruiting
    • Department of Hematology, Hospitalsenheden Vest
    • Principal Investigator: Robert Schou Pedersen
  • Odense, Denmark, 5000
    • Recruiting
    • Department of Hematology, Odense University Hospital
    • Principal Investigator: Niels Abildgaard, MD
  • Roskilde, Denmark, 4000
    • Recruiting
    • Department of Hematology, Roskilde Hospital
    • Principal Investigator: Ulf Christian Frølund, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Henrik Gregersen
• Collaborators: Danish Myeloma Study Group
• Investigators: Principal Investigator: Henrik Gregersen, MD, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (Estimate): December 8, 2015

Study Record Updates

• Last Update Posted (Estimate): December 8, 2015
• Last Update Submitted That Met QC Criteria: December 4, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Infection; Multiple Myeloma; Clarithromycin; Trimethoprim-Sulfamethoxazole Combination
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Clarithromycin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: DMSG#01/12; 2012-004424-38 (EudraCT Number)