A Phase III Multicenter Study Of Valganciclovir For The Prevention Of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation
16 Years
N/A
Both
Infection
Trial Information
A Phase III Multicenter Study Of Valganciclovir For The Prevention Of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation
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.
Inclusion Criteria
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
Type of Study:
Interventional
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
Authority:
United States: Federal Government
Study ID:
1577.00
NCT ID:
NCT00016068
Start Date:
January 2001
Completion Date:
September 2007
Related Keywords:
- Infection
- infection
- Cytomegalovirus Infections
Name | Location |
|---|---|
| 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 |
