Official Title: “An Investigator Initiated Prospective Randomized, Controlled Pilot Study in Order to Evaluate the Place of Valganciclovir in Prevention of Cytomegalovirus Reactivation Following Allogeneic Stem Cell Transplantation”

The rationale for this protocol is based on the need to assess if the current post stem cell transplantation CMV prophylaxis strategies (e.g. high-dose acyclovir plus pre-emptive treatment) can be improved by the use of valganciclovir. CMV is the most common viral infection following stem cell transplantation, causing significant morbidity and mortality.

Furthermore, CMV has been shown to be associated with a number of indirect effects in SCT recipients including allograft dysfunction, acute and chronic graft versus host disease (GVHD). Valganciclovir is shown to be more active than oral ganciclovir, and as good as intravenous (i.v.) ganciclovir in treating newly diagnosed CMV retinitis. The use of valganciclovir for CMV prophylaxis post stem cell transplantation was never tested in controlled study. The investigators therefore suggest a prospective, randomized study to evaluate the efficacy and safety of valganciclovir compared with acyclovir for prevention of CMV disease in allogeneic stem cell transplantation recipients.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2009

Cytomegalovirus (CMV), the most common viral infection following stem cell transplantation (SCT), causes significant morbidity and mortality. It can result in CMV pneumonitis, hepatitis, encephalitis and gastrointestinal disease, as well as fever and neutropenia.

Furthermore, CMV has been shown to be associated with a number of indirect effects in SCT recipients including reduced long-term patient survival, increased risks of opportunistic infections, allograft dysfunction, acute and chronic graft vs. host disease (GVHD). SCT patients at highest risk are seronegative donors, matched unrelated donors, SCT with T-cell depletion, patients after cord blood SCT, and patients with GVHD.

Valganciclovir, a valine ester pro-drug of ganciclovir, was developed to overcome the limitations of oral and i.v. ganciclovir, with a single once-daily 900 mg oral dose providing comparable plasma ganciclovir exposures to those achieved with 5 mg/kg i.v. ganciclovir. Its bioavailability is up to 10-fold higher than that of oral ganciclovir (same as above). There is already extensive clinical experience with valganciclovir in AIDS patients, where it has proved as effective as i.v. ganciclovir in treating newly diagnosed CMV retinitis, and in patients after solid organ transplant but no comparative data exists in patients after SCT.

We therefore planned a prospective, randomized study to evaluate the efficacy and safety of valganciclovir compared with acyclovir for prevention of CMV disease in SCT recipients.

Intervention(s) in this Clinical Trial

• Drug: Valganciclovir
  • Valganciclovir
• Drug: Acyclovir
  • Acyclovir

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • PO Valganciclovir
• Active Comparator: 2
  • PO Acyclovir

Primary Measures

• Prevention of CMV reactivation
  • Time Frame: 100d
    Safety Issue?: No

Secondary Measures

• Occurrence of CMV disease
  • Time Frame: 6m
    Safety Issue?: No
• Overall survival
  • Time Frame: 6m
    Safety Issue?: No
• Occurrence of GVHD
  • Time Frame: 6m
    Safety Issue?: Yes
• Occurrence of other infections
  • Time Frame: 6m
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Undergoing allogeneic SCT from a matched related or unrelated donor without T cell depletion.
• 2. Had an acceptable engraftment.
• 3. Can take oral medications within 10 days of engraftment.
• 4. Either the recipient or donor (or both) is CMV seropositive.

Exclusion Criteria:

• 1. Not fulfilling the inclusion criteria.
• 2. History of CMV infection or disease.
• 3. Anti-CMV therapy within the past 15 days.
• 4. Severe, uncontrolled diarrhea.
• 5. Both recipient and donor are CMV seronegative.
• 6. Evidence of malabsorption.
• 7. Inability to comply with study requirements.
• 8. Known hypersensitivity or other contraindication to ganciclovir or valganciclovir.
• 9. Pregnant or lactating patients.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 14 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Hadassah Medical Organization

Overall Clinical Trial Officials and Contacts

Michael Y Shapira, MD Principal Investigator Hadassah Medical Organization, Jerusalem, Israel  

Overall Contact: Michael Y , Shapira, MD 00 972 2 6778351 shapiram@hadassah.org.il

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00330018

Study ID Number: MYS-03-HMO-CTIL

ClinicalTrials.gov Identifier: NCT00330018

Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration