Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients
- Registration Number
- NCT00411645
- Lead Sponsor
- Shire
- Brief Summary
The purpose of this research study is to investigate whether or not maribavir is safe and effective for preventing CMV disease when taken by mouth for up to 12 weeks in patients who have had a stem cell transplant.
- Detailed Description
Cytomegalovirus (CMV) infections remain a significant problem following various types of transplants that are associated with strong immunosuppressive therapy. Maribavir is a new oral anti-CMV drug with a novel mechanism of action compared to currently available anti-CMV drugs. This study will test the safety and efficacy of maribavir for the prevention of CMV disease when given as prophylaxis for up to 12 weeks following allogeneic stem cell transplant.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 681
- Allogeneic stem cell transplant recipient
- Recipient or donor CMV seropositive
- Have transplant engraftment
- Able to swallow tablets
- CMV organ disease
- HIV infection
- Use of other anti-CMV therapy post-transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B placebo - A maribavir -
- Primary Outcome Measures
Name Time Method Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation 6 months post-transplant All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
- Secondary Outcome Measures
Name Time Method Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant 6 months post-transplant All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Percent of Participants With Acute Graft-Versus-Host Disease (GVHD) Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant) Analysis of acute GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for acute GVHD. The percentage reported is for the occurrence of any grade of acute GVHD.
Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD) Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant) Analysis of chronic GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for chronic GVHD. The percentage reported is for the occurrence of any grade of chronic GVHD.
Plasma Concentration of Maribavir During Treatment 12 hours post-dose after 1 and 4 weeks of treatment Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation 100 days post-transplant All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Number of Participants Who Died Within 12 Months Post-Transplantation Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant) Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment 12 hours post-dose after 1 and 4 weeks of treatment Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of VP 44469, a metabolite of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation 6 months post-transplant All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay or (2) CMV DNA polymerase chain reaction (PCR). CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Number of Participants With Investigator-determined CMV Disease Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant) CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation 12 months post-transplant All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.
Trial Locations
- Locations (97)
University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Jeanes Hospital - Temple
🇺🇸Philadelphia, Pennsylvania, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Ireland Cancer Center Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Methodist Hospital
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Arkansas Myeloma Institute
🇺🇸Little Rock, Arkansas, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Massachusettes General
🇺🇸Boston, Massachusetts, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Essen
🇩🇪Essen, Germany
Hopital Haut-Leveque
🇫🇷Pessac, France
Univ. Clinic Dresden
🇩🇪Dresden, Germany
University Clinic of Dresden
🇩🇪Dresden, Germany
The Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke Medical Center
🇺🇸Durham, North Carolina, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
UCSD Moores Center
🇺🇸La Jolla, California, United States
Northwestern University Medical Center
🇺🇸Chicago, Illinois, United States
St Francis Hospital
🇺🇸Beech Grove, Indiana, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
New York Presbyterian Hospital,Weill Cornell Medical Center
🇺🇸New York, New York, United States
Thomas Jefferson
🇺🇸Philadelphia, Pennsylvania, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
VA Puget Sound Health Center
🇺🇸Seattle, Washington, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Vanderbilt Medical Center
🇺🇸Nashville, Tennessee, United States
Latter Day Saints Hospital
🇺🇸Salt Lake City, Utah, United States
Hopital Hotel Dieu
🇫🇷Nantes, Cedex 1, France
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Johannes-Gutenberg University
🇩🇪Mainz, Germany
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Wayne State Medical Center
🇺🇸Detroit, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Mayo Clinic College of Medicine
🇺🇸Rochester, Minnesota, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Sciences University
🇺🇸Portland, Oregon, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Wake Forest Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Hopital l'Enfant Jesus
🇨🇦Quebec, Canada
City of Hope Medical Center
🇺🇸Duarte, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Scripps Green Hospital
🇺🇸La Jolla, California, United States
Shands Hospital
🇺🇸Gainesville, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Greenbaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Loyola University
🇺🇸Maywood, Illinois, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Western Pennsylvania Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Cliniques Universitaires St,Luc Dept Hematology
🇧🇪Brussels, Belgium
ZNA Stuivenberg
🇧🇪Antwerp, Belgium
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States
AZ Sint Jan, Department of Hematology
🇧🇪Brugge, Belgium
UZ Gasthuisberg
🇧🇪Leuven, Belgium
CHU Sart -Tilman Department of Medicine, Hematology
🇧🇪Liege, Belgium
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
McMaster University Medical Center
🇨🇦Hamilton, Ontario, Canada
Ottawa General Campus
🇨🇦Ottawa,, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Institut Paoli Calmettes
🇫🇷Marseille Cedex 9, France
Hopital Henri Mondor
🇫🇷Créteil, France
Edouard Herriot Hopital
🇫🇷Lyon, Cedex 03, France
Hopital St. Louis
🇫🇷Paris Cedex 10, France
University of Hamburg-Eppendorf
🇩🇪Hamburg, Germany
University of Freiburg
🇩🇪Freiburg, Germany
Hannover, Medizinische Hochschule
🇩🇪Hannover, Germany
University of Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Koeln, Clinic I for internal Medicine
🇩🇪Koeln, Germany
University Clinic of Ulm
🇩🇪Ulm, Germany
Careggi University Hospital
🇮🇹Firenze, Italy
University of San Martino Hospital
🇮🇹Genova, Italy
San Raffaele del Monte Tabor
🇮🇹Milano, Italy
Bianchi-Melacrino-Morelli Hospital
🇮🇹Reggio Calabria, Italy
Pescara Hospital
🇮🇹Pescara, Italy
Barcelona Hospital
🇪🇸Barcelona, Spain
Karolinska University Hospital
🇸🇪Huddinge, Stockholm, Sweden
University of Salamanca
🇪🇸Salamanca, Spain
Duran i Reynals Hospital
🇪🇸Barcelona, Spain
Sahlgrenska University Hospital
🇸🇪Goteborg, Sweden
Karolinska University Hospital,Huddinge
🇸🇪Stockholm, Sweden
Royal Free Hospital
🇬🇧London, United Kingdom
Akademiska Sjukhuset, Dept Hematology
🇸🇪Uppsala, Sweden
Hammersmith Hospital
🇬🇧London, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Mount Sinai Hospital
🇺🇸New York, New York, United States
University Medical Center University of Louisville Hospital
🇺🇸Louisville, Kentucky, United States
University of North Carolina Hospital
🇺🇸Chapel Hill, North Carolina, United States
Medical College of Virginia
🇺🇸Richmond, Virginia, United States