Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients
Cytomegalovirus Infection
About this trial
This is an interventional prevention trial for Cytomegalovirus Infection focused on measuring Allogeneic stem cell transplant, CMV seropositive (R+), transplant
Eligibility Criteria
Inclusion Criteria
For inclusion into the study, all prospective subjects were required to fulfill all of the following criteria (as applicable):
- Were aged ≥18 years. Males must have been able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study.
- Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects).
- Were less than 30 days post qualifying transplant.
- Had evidence of engraftment before randomization and receiving their first dose of study drug.
- Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] events).
- Were willing and able to understand and provide written informed consent.
- To the best of his or her knowledge, were willing and able to participate in all required study activities for the duration of the study.
Exclusion Criteria
Subjects meeting any of the following exclusion criteria were to be excluded from participation in the study:
- Females who were pregnant or currently nursing.
- Had a body mass index >35 kg/m2. [Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.]
- Had hypersensitivity to cidofovir (CDV) or brincidofovir.
- Recipients for whom the current, predose clinical course of CMV infection suggested that the investigator would not be able to withhold treatment for CMV for a minimum of 5, but preferably 7 days following the subject's first dose of study drug.
Received any of the following:
- Ganciclovir, valganciclovir, foscarnet or CDV within 14 days prior to enrollment;
- Any anti-CMV therapy following transplantation (including Cytogam®1);
- Any CMV vaccine;
- Any investigational drug with antiviral activity against double-stranded DNA (dsDNA) viruses within 14 days prior to enrollment. [Note: An investigational drug was defined as a drug that was not approved for any indication by the Food and Drug Administration.]; or
- Any other investigational drug (i.e., those without any "anti-dsDNA virus" activity; e.g., anti-influenza compounds) within 14 days prior to enrollment without the prior written consent of the medical monitor. The use of investigational drugs in certain circumstances was added per Protocol Amendment 1 dated 15 January 2010.
- Received high dose acyclovir (>2000 mg total oral daily dose or >5 mg/kg intravenously 3 times daily) or valacyclovir (Valtrex; >3000 mg total daily dose) at the time of dosing.
- Were diagnosed with active CMV disease within 6 months prior to enrollment; patients with CMV DNAemia requiring intervention with antiviral therapy at the time of enrollment.
- Were HIV positive; patients with active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.
- Received another allogeneic HCT within the past 2 years, other than the qualifying HCT.
- Had renal insufficiency as evidenced by glomerular filtration rate (GFR) <30 mL/min.
- Had a current diagnosis of hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the subject to any one of these conditions.
- Had hepatic dysfunction as evidenced by alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN) or direct bilirubin >2.5 x the ULN.
- Had any of the following active autoimmune disorders: myasthenia gravis, Addison's disease, Wegener's granulomatosis, primary biliary cirrhosis, bullous pemphigoid, autoimmune hemolytic anemia, autoimmune hepatitis, multiple sclerosis, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, lupus erythematosus, dermatomyositis, polymyositis, or vasculitis.
- Had active solid tumor malignancies with the exception of basal cell carcinoma or the condition under treatment (e.g., lymphomas).
- Had 1 or more episode of hyperglycemic coma or diabetic ketoacidosis within the 6 months prior to enrollment.
- Had cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study.
- Had Grade 3 or 4 graft versus host disease of the GI tract; subjects with any GI disease that would, in the judgment of the investigator, preclude the subject from taking or absorbing oral medication (e.g. clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, or any condition expected to require abdominal surgery during the course of study participation).
- Any other condition including abnormal laboratory values that would have, in the judgment of the investigator, put the subject at increased risk for participating in the trial, or interferes with the conduct of the trial.
Sites / Locations
- The University of Alabama at Birmingham
- Moores UCSD Cancer Center
- UCLA Medical Center
- University of Colorado Denver
- Winship Cancer Institute at Emory University
- University of Chicago Medical Center
- Brigham and Womens Hospital, Division of Infectious Disease
- University of Michigan Medical School
- Harper University Hospital
- University of Minnesota Medical Center
- Nebraska Medical Center
- Hackensack University Medical Center
- Montefiore Medical Center Oncology
- Mt. Sinai School of Medicine
- Memorial Sloan Kettering Cancer Center
- University of Rochester Medical Center
- UNC Health Care Center
- Duke University Medical Center
- Wake Forest University School of Medicine
- The Cleveland Clinic
- Oregon Health and Science University
- Baylor University Medical Center
- UT Southwestern Medical Center at Dallas
- University of Texas, MD Anderson Cancer Center
- Utah Cancer Specialists - Intermountain Healthcare
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
Placebo
Brincidofovir
Cohort 1 = 40 mg of matching placebo administered once weekly (QW) Cohort 2 = 100 mg of matching placebo administered QW Cohort 3 = 200 mg of matching placebo administered QW Cohort 4 = 200 mg of matching placebo administered twice weekly (BIW) Cohort 4A = 100 mg of matching placebo administered BIW
Cohort 1 = 40 mg brincidofovir (BCV) administered once weekly (QW) Cohort 2 = 100 mg BCV administered QW Cohort 3 = 200 mg BCV administered QW Cohort 4 = 200 mg BCV administered twice weekly (BIW) Cohort 4A = 100 mg BCV administered BIW