Valganciclovir to Prevent Cytomegalovirus Infection in Patients Following Donor Stem Cell Transplantation

Infection Clinical Trial

Official title:

A Phase III Multicenter Study Of Valganciclovir For The Prevention Of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00016068
• Other study ID #: 1577.00
• Secondary ID: FHCRC-1577.00MSK
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2001
• Last updated: May 14, 2010
• Start date: January 2001
• Est. completion date: September 2007

Study information

• Verified date: May 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Antivirals such as valganciclovir act against viruses and may be effective in preventing cytomegalovirus. It is not yet known if valganciclovir is effective in preventing cytomegalovirus.

PURPOSE: This randomized phase III trial is studying valganciclovir to see how well it works in preventing cytomegalovirus in patients who have undergone donor stem cell transplantation.

Description:

OBJECTIVES:

Primary

• Compare cytomegalovirus (CMV) disease and non-CMV invasive infection-free survival in patients undergoing allogeneic hematopoietic stem cell transplantation treated with valganciclovir vs placebo.

• Compare the incidence of CMV disease in patients treated with these drugs.

• Compare the incidence of other severe invasive bacterial and fungal infections and overall survival in patients treated with these drugs.

Secondary

• Compare the incidence of CMV infection or disease at baseline and at days 270 and 640 after allogeneic hematopoietic stem cell transplantation in patients treated with these drugs.

• Compare the incidence of herpes simplex virus and varicella-zoster virus infections at baseline and day 270 in patients treated with these drugs.

• Determine the safety of valganciclovir in these patients.

• Compare the quality of life of patients treated with these drugs.

• Compare CMV-specific immune reconstitution in patients treated with these drugs.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, prior neutropenia (yes vs no), and presence of refractory graft-versus-host disease requiring secondary therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral valganciclovir daily.

• Arm II: Patients receive oral placebo daily. Treatment begins around day 80-120 post-transplantation and continues until day 270 post-transplantation in the absence of active infection or unacceptable toxicity. Patients developing active cytomegalovirus (CMV) infection receive induction doses of ganciclovir IV or open-label oral valganciclovir for 1 week followed by open-label oral valganciclovir maintenance dosing until CMV can no longer be detected.

Quality of life is assessed at baseline and days 180 and 270 post-transplantation.

Patients are followed at days 400, 520, and 640 post-transplantation.

PROJECTED ACCRUAL: A total of 184 patients (92 per treatment arm) will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Have undergone allogeneic peripheral blood stem cell, cord blood, or marrow transplantation (related or unrelated, T-cell depleted or non-T-cell depleted, CD34-selected or non-selected, or myeloablative or non-myeloablative) within the past 80-120 days

• Positive pre-transplantation cytomegalovirus (CMV) serology of recipient and/or donor

• Seropositive recipients with one of the following:

• CMV infection before day 80, as determined by:

• pp65 antigenemia

• CMV DNA in plasma

• Peripheral blood leukocytes (PBL) or whole blood at any level detected by polymerase chain reaction or hybrid capture

• CMV pp67 mRNA

• CMV viremia by blood culture

• Surveillance bronchoalveolar lavage (culture or cytology)

• CMV disease more than 6 weeks prior to enrollment

• Presence of graft-versus-host disease (GVHD) at enrollment

• Acute GVHD that requires treatment with systemic corticosteroids of doses greater than 0.5 mg/kg OR

• Chronic clinically extensive GVHD requiring treatment with corticosteroids

• Continuous prophylaxis with ganciclovir, foscarnet, or cidofovir between engraftment and day 80 OR

• Seronegative recipient with seropositive donor who has CMV infection before day 80

• No rising or uncontrolled CMV load (pp65 antigenemia levels no greater than 1/slide or no greater than 100 copies of CMV DNA per mL of plasma or per million PBL allowed)

• No CMV disease within 6 weeks prior to randomization

• No leukemic relapse

• Cytogenetic or molecular relapse allowed

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Not specified

Life expectancy:

• At least 2 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3 for at least 1 week prior to enrollment

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 2.5 mg/mL

Other:

• No hypersensitivity to ganciclovir or valganciclovir

• No uncontrolled diarrhea or severe gastrointestinal disease that would preclude oral medication

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 90 days after study participation

• HIV negative

• Proficient in English

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• Not specified

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Prior ganciclovir, foscarnet, cidofovir, high-dose acyclovir, or valacyclovir as prophylaxis or preemptive therapy allowed

• No concurrent prophylactic foscarnet, cidofovir, or ganciclovir (IV or oral)

• No concurrent prophylactic high-dose acyclovir (more than 800 mg twice daily), valacyclovir (more than 500 mg twice daily), cidofovir (more than 0.5 mg/kg per week), or famciclovir (more than 500 mg/day) except for limited treatment courses at higher doses for varicella-zoster virus infections

• Concurrent low-dose (= 0.5 mg/kg per week) cidofovir allowed for limited treatment courses

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Infection

Intervention

Drug:
• ganciclovir

• valganciclovir

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Late cytomegalovirus infection by plasma PCR positivity