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

Phase 3
16 Years
Not Enrolling

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Trial Information

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



- 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.


- 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

- 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

Inclusion Criteria


- 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

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

- Seronegative recipient with seropositive donor who has CMV infection before day

- 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



- 16 and over

Performance status:

- Not specified

Life expectancy:

- At least 2 weeks


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


- Not specified


- Creatinine no greater than 2.5 mg/mL


- No hypersensitivity to ganciclovir or valganciclovir

- No uncontrolled diarrhea or severe gastrointestinal disease that would preclude oral

- Not pregnant or nursing

- Negative pregnancy test

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

- HIV negative

- Proficient in English


Biologic therapy:

- See Disease Characteristics


- Not specified

Endocrine therapy:

- See Disease Characteristics


- Not specified


- Not specified


- 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

Type of Study:


Study Design:

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

Outcome Measure:

Late cytomegalovirus infection by plasma PCR positivity

Principal Investigator

Michael Boeckh, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center


United States: Federal Government

Study ID:




Start Date:

January 2001

Completion Date:

September 2007

Related Keywords:

  • Infection
  • infection
  • Cytomegalovirus Infections



Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Memorial Sloan-Kettering Cancer Center New York, New York  10021
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
City of Hope Comprehensive Cancer Center Duarte, California  91010
M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030
University of Florida Shands Cancer Center Gainesville, Florida  32610-0232