Valganciclovir in Prevention of Cytomegalovirus (CMV) Reactivation Following Allogeneic-Stem Cell Transplantation (SCT)

Bone Marrow Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00330018
• Other study ID #: MYS-03-HMO-CTIL
• Status: Completed
• Phase: Phase 3
• First received: May 24, 2006
• Last updated: April 19, 2015
• Start date: February 2006
• Est. completion date: April 2010

Study information

• Verified date: August 2009
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bone Marrow Transplantation
• Cytomegalovirus

Intervention

Drug:
• Valganciclovir
Valganciclovir
• Acyclovir
Acyclovir

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization,	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevention of CMV reactivation		100d	No
Secondary	Occurrence of CMV disease		6m	No
Secondary	Overall survival		6m	No
Secondary	Occurrence of GVHD		6m	Yes
Secondary	Occurrence of other infections		6m	Yes