Trial of Preemptive Treatment With Oral Valganciclovir Compared With Intravenous (IV) Ganciclovir for Cytomegalovirus Infection After Bone Marrow or Peripheral Blood Stem Cell Transplant

Randomized Trial of Preemptive Treatment With Oral Valganciclovir Compared With IV Ganciclovir for Cytomegalovirus Infection After Bone Marrow or Peripheral Blood Stem Cell Transplant

The purpose of this trial is to determine if preemptive therapy with oral valganciclovir is as effective as intravenous ganciclovir in clearing cytomegalovirus (CMV) viremia as determined by quantitative CMV polymerase chain reaction (PCR) assay in patients who have undergone bone marrow or peripheral blood stem cell transplant.

Study Overview

• Status: Terminated
• Conditions: Cytomegalovirus Infections
• Intervention / Treatment: Drug: Ganciclovir; Drug: Valganciclovir

Detailed Description

• To study the effect of preemptive therapy with IV ganciclovir and PO valganciclovir as determined by quantitative CMV PCR.
• To determine the incidence of CMV disease and CMV related mortality following preemptive treatment with oral valganciclovir and IV ganciclovir.
• To compare the incidence of recurrent CMV viremia after treatment with PO valganciclovir to that seen after treatment with IV ganciclovir.
• To determine the toxicity profile of valganciclovir.
• To screen for mutations in the UL97 gene in patients who have increasing CMV viral loads after 14 days of treatment.
• To determine if patients treated with PO valganciclovir have ganciclovir drug levels which are equivalent to those seen in historical control subjects treated with PO valganciclovir.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients receiving allogeneic peripheral blood stem cell transplant from either a related or unrelated donor at Washington University Medical Center.
• An initial episode of CMV viremia.

• At the time of randomization:

  • ANC greater than or equal to 1000
  • Age greater than or equal to 18
  • Adequate renal function with creatinine clearance greater than 10 ml/min
  • Total bilirubin less than or equal to 3.0

Exclusion Criteria:

• Current GI graft versus host disease grade III-IV
• Development of CMV disease prior to or at the time of the first detection of CMV viremia by PCR
• Uncontrolled emesis or diarrhea (greater than or equal to 4 episodes per day) for 2 consecutive days
• Pregnant or nursing female patient
• Known hypersensitivity to ganciclovir

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; IV ganciclovir (5mg/kg every 12 hours for 7 days followed by 5mg/kg every 24 hours for 7 days. If CMV viral load <5000 copies/ml after 14 days then 5mg/kg every 24 hours for a total of 21 total days of therapy. If CMV viral load >5000/ml but less than index viral load after 14 days then 5mg/kg every 24 hours for a total of 28 total days of therapy. If CMV viral load >= index viral load after 14 days then 5mg/kg every 12 hours for 7 days. If repeat CMV viral load is <= the previous CMV viral load then 5mg/kg every 12 hours for an additional 7 days.	Drug: Ganciclovir
Experimental: Group B; PO valganciclovir (900 mg every 12 hours for 7 days followed by 900 mg every 24 hours for 7 days. If CMV viral load <5000 copies/ml after 14 days then 900 mg every day until 21 total days of therapy. If CMV viral load >5000 copies/ml after 14 days but less than the index viral load then 900 mg every day until 28 total days of therapy. If CMV viral load >= the index viral load 900 mg every 12 hours for 7 days, if CMV viral load <= to previous viral load then 900 mg every 12 hours for another 7 days.	Drug: Valganciclovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
If preemptive therapy with oral valganciclovir is as effective as intravenous ganciclovir in clearing CMV viremia as determined by quantitative CMV PCR assay in patients who have undergone allogeneic bone marrow or peripheral stem cell transplant.	Clearance of CMV viremia will be defined as CMV viral load less than 5,000 copies/ml of whole blood.	4 weeks from start of therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of preemptive therapy with IV ganciclovir and PO valganciclovir as determined by quantitative CMV PCR.	6 months
Incidence of CMV disease and CMV related mortality following preemptive treatment with oral valganciclovir and IV ganciclovir.	6 months
Compare the incidence of recurrent CMV viremia after treatment with PO valganciclovir to that seen after treatment with IV ganciclovir.	6 months
Toxicity profile of valganciclovir	6 months
Mutations in the UL97 gene in patients who have increasing CMV viral loads after 14 days of treatment	14 days
Determine if patients treated with PO valganciclovir have ganciclovir drug levels which are equivalent to those seen in historical control subjects treated with PO valganciclovir.	6 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: October 17, 2005
• First Submitted That Met QC Criteria: October 17, 2005
• First Posted (Estimate): October 18, 2005

Study Record Updates

• Last Update Posted (Estimate): July 23, 2013
• Last Update Submitted That Met QC Criteria: July 22, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: post transplant; Any patient receiving an allogeneic bone marrow or peripheral blood stem cell transplant at Washington University Medical Center
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Valganciclovir; Ganciclovir; Ganciclovir triphosphate
• Other Study ID Numbers: 04-0274