Study to Evaluate the Safety and Efficacy of Telavancin in the Treatment of Gram Positive Bloodstream Infections in Cancer Patients

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if Vibativ (telavancin) can help to control blood stream infections (BSIs). The safety of this treatment will also be studied. Objectives: Evaluate the clinical efficacy and safety of Telavancin given for treatment of gram positive bacteremia in cancer patients (including neutropenics).

Detailed Description
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The Study Drug: Telavancin is an antibiotic designed to treat a variety of bacterial infections that are difficult to treat. Central Venous Catheter (CVC): A CVC is a sterile flexible tube could have been placed into a large vein while you were under local anesthesia. If you have a certain type of infection, your doctor may decided to remove or exchange your CVC. The decision to remove or exchange the CVC and timing of the placement of the new CVC will be decided by your primary doctor. If you are to get a new CVC, your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form. Study Treatment: If you are found to be eligible to take part in this study, you will receive telavancin by vein over a period of 60 minutes once daily for at least 7 days and for up to 6 weeks. How long you receive the study drug will depend on the type of bacterial infection that you have and if your doctor thinks you may have a complicated bacterial infection of the blood. If the doctor thinks that you have a mixed infection (2 or more certain types of bacteria), you may also be given another type of antibiotic (such as aztreonam, cefepime, imipenem, meropenem, ciprofloxacin hydrochloride, bactrim, piperacillin/tazobactam and/or amoxicillin/clavulanate). If the doctor thinks it is needed, you will have an echocardiogram to check your heart function. This test will only be performed if you have a specific type of infection (to make sure you do not have inflammation in the lining of the heart). You will be asked about medications you are taking. If you are discharged from the hospital before completing the study drug, you will be able to take the drug as an outpatient. Your primary doctor may arrange for you to receive medication at M. D. Anderson. Study Visits: Once a week: Blood (about 1 tablespoon) will be drawn for routine tests. It may be drawn from the CVC, if the CVC is still in place. The CVC exit site will be checked at each visit until you have no more signs or symptoms of infection. You will be asked about any symptoms or illnesses that you may have had since your last visit. Every other day, blood (about 1 tablespoon) will be drawn to check for the infection until it no longer shows signs of infection. Kidney function will be monitored by performing a blood test every 2 days for the first week and weekly after that. Length of Study: You can receive the study drug for up to 6 weeks. You will be taken off this study if the infection gets worse or any intolerable side effects occur. End-of-Study Visit and Follow-up Visit: You will need to return to MD Anderson for your end of treatment visit, within 7 days after you last dose of study drug. The end-of-study visit will occur within 7 days after your last dose of the study drug. The follow-up visit will occur about 32 days (about 1 month) after your last dose of the study drug. At each of these visits, you will have the following exams/procedures performed. You will have a physical exam, including measurement of your vital signs. Blood (about 1 tablespoon) will be drawn for routine tests and to check for bacterial infection. The blood sample may be drawn from the CVC, if the CVC is still in place. The CVC exit site will be examined. You will be asked about any symptoms or illnesses that you may have had since your last visit. You will be asked about any drugs or therapies that you may be taking until the end of your treatment. If your infection recurs during the follow-up period, and if the doctor thinks it is needed, you will have an echocardiogram to check your heart function and to make sure you do not have inflammation in the lining of the heart. This is an investigational study. Telavancin is FDA approved and commercially available for the treatment infections of the skin and soft tissue. Its use to treat blood infections in this study is investigational. Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Official Title
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Phase II, Open-Label Pilot Study to Evaluate the Safety and Efficacy of Telavancin in the Treatment of Gram Positive Bloodstream Infections in Cancer Patients

Conditions
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Infection, Bacteremia

Intervention / Treatment
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* Drug: Telavancin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with probable or definite diagnosis of uncomplicated gram positive bacteremia that have at least one positive blood culture including 20 patients with Staphylococcus aureus and the other 20 patients will include any of the following organism ( CNS, Enterococci, streptococci, pneumococci, Corynebacterium, and Propionibacterium or Bacillus species).If the positive blood culture involves a commensal skin organism such as CNS, Corynebacterium, Propionibacterium, Micrococcus and Bacillus, then at least > 100 colonies/ml will be required or a time to positivity =/< 16 hours (as it has been shown to reflect a high grade bacteremia), or two positive blood cultures. (Time to positivity of a blood culture bottle is recorded in the microbiology laboratory by the automatic culture detector (Bactec 9240 and Bactec Plus Aerobic/F; Becton Dickinson) which records culture positivity every 15 min according to changes in fluorescence related to microbial growth). Patients must have at least two signs of sepsis from the list below, in any combination at any time, within 48 hours prior to Telavancin therapy: a. Core temperature =/>38.0 degrees C or =/<36.0 degrees C, measured orally, rectally, tympanic ally or via a central catheter. If auxiliary add 0.5 degrees C to the measured temperature; b. Pulse rate =/> 100 beats/min.; c. Respiratory rate =/> 20/min.; d. WBC count =/>12,000/mm^3, =/<4,000/mm or differential count showing >10% band forms; e. Systolic blood pressure =/<90 mm Hg. Patient will still be eligible for the study if the participants white blood cell count (WBC) is outside normal limits due to chemotherapy treatment or underlying conditions. Male or non-pregnant, non-lactating females with an age of greater than or equal to 18 years. Signed informed consent. Female patients must be at no risk for pregnancy for one of the following reasons: - Postmenopausal for at least one year - Post-hysterectomy and/or post-bilateral ovariectomy - If of childbearing potential, having a negative serum human chorionic gonadotropin (hCG) pregnancy test with in 5 days prior to enrollment and be using a highly effective method of birth control throughout the course of the study. Reliable sexual abstinence throughout the course of the study is acceptable as a highly effective method of birth control for the purposes of this study. Exclusion Criteria: Estimated Serum Creatinine Clearance <30 mL/min (according to Cock-Gault-formula using ideal body weight) at the time gram positive bacteremia was diagnosed unless the patient is on dialysis. Bilirubin >4x the upper limit of normal at the time gram positive bacteremia was diagnosed. Treatment with an antibiotic, such as vancomycin, linezolid, tigecycline or Telavancin, effective against resistant gram positive bacterial infections, such as methicillin resistant staphylococci, for more than 48 hours within 72 hours of study medication initiation, unless treatment failed that is defined as a persistent fever and/or leukocytosis for 72 hours or longer of appropriate antibiotics treatment. History of hypersensitivity to lipoglycopeptides. Presence of deep-sited intravascular source of infection with same organism cultured from blood, e.g. endocarditis (as evidenced by vegetations on an echocardiogram), or septic thrombosis. Presence of a prosthetic valve. Oliguria defined as urine output of <20 cc/hour averaged over 24 hours.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telavancin<br>10 or 7.5 mg/kg intravenous daily | Drug: Telavancin<br>* 10 mg/kg by vein once daily for patients with a creatinine clearance of more than 50 ml/min, and a dose of 7.5 mg/kg once daily for patients with a creatinine clearance of 30-50 ml/min.<br>* Other names: Vibativ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Clinical Response to Telavancin | Clinical response assessed: Cure (No fever/chills or symptoms + eradication causing organism); Improvement (Resolution local/systemic symptoms + no new systemic antibacterial treatment); Failure (IF one or more following: Persistence 1+ symptoms [fever/chills] + new systemic anti gram positive treatment, > 72 hours after initiation study drug; or Relapse within 1 month completing antibiotic therapy; or Development of deep-seated infection not previously assessed); Indeterminate (clinical signs and symptoms cannot be assessed). | From baseline up to 6 weeks, assessed every 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gram Positive Bloodstream Infections, Sepsis, Staphylococcus aureus, Enterococci, Streptococci, Pneumococci, Corynebacterium, Propionibacterium or Bacillus species, Telavancin, Vibativ