Official Title: “A Phase III Multicenter Study of Cytomegalovirus Prophylaxis With Valacyclovir for the Prevention of Serious Fungal and Bacterial Infections Among Cytomegalovirus Seronegative Recipients of Cytomegalovirus Seropositive Sx Stem Cell Transplants”

RATIONALE: Antivirals such as valacyclovir act against viruses and may be effective in preventing cytomegalovirus. It is not yet known if valacyclovir is effective in preventing cytomegalovirus in patients undergoing stem cell transplantation.

PURPOSE: Randomized phase III trial to determine the effectiveness of valacyclovir in preventing cytomegalovirus in patients who are undergoing donor stem cell transplantation.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

OBJECTIVES: - Compare the occurrence of serious invasive fungal or bacterial infections during the first 270 days after transplantation in cytomegalovirus (CMV)-negative patients receiving a CMV-positive allogeneic stem cell transplantation and valacyclovir or placebo. - Compare the occurrence of primary CMV infection within the first 100 days after transplantation in patients treated with these regimens. - Compare the survival of these patients at 100 days and 270 days post-transplantation. - Compare the occurrence of CMV disease at day 100 and day 270 post-transplantation in patients treated with these regimens. - Compare the safety of these regimens in these patients. - Correlate the presence of CMV in stem cell product with post-transplantation CMV infection in these patients. - Determine if subclinical CMV infection results in a virus-specific immune response (humoral and cellular) in these patients. - Compare the quality of life of patients treated with these regimens. - Compare resource utilization (e.g., rates of hospitalization, number of days alive out of the hospital, days in the intensive care unit, days on mechanical ventilation, use of antimicrobials and filgrastim [G-CSF], and number of invasive procedures) in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and type of transplantation (matched related vs mismatched/unrelated). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral valacyclovir 4 times daily beginning with transplantation conditioning (usually day -5) and continuing until day 100 after transplantation.

Patients receive high-dose acyclovir, instead of valacyclovir, IV every 8 hours beginning on day -1 and continuing until oral medications are tolerated. Allogeneic stem cells are infused on day 0. - Arm II: Patients receive oral or IV placebo on the same schedule as in arm I. Quality of life is assessed at baseline and on days 50 and 100.

Patients are followed every 2 weeks for 6 months.

PROJECTED ACCRUAL: A total of 115-230 patients (58-115 per treatment arm) will be accrued for this study within 2 years.

Intervention(s) in this Clinical Trial

• Drug: acyclovir
• Drug: acyclovir sodium
• Drug: valacyclovir

DISEASE CHARACTERISTICS:

• Disease requiring one of the following types of stem cell transplantation:
• First myeloablative allogeneic peripheral blood stem cell
• Unrelated cord blood
• Bone marrow
• Related or unrelated donor
• T-cell depleted or non-T-cell depleted
• CD34 selected or non-selected
• Patient must be cytomegalovirus (CMV)-seronegative and donor must be CMV-seropositive
• No transplantation with nonmyeloablative regimens, including any of the following:
• Fludarabine and total body irradiation (TBI) (2 Gy or less)
• TBI alone (2 Gy)
• Fludarabine, cytarabine, and idarubicin
• Fludarabine and melphalan (140 mg/m^2 or less)
• No definite or probable pre-transplantation diagnosis of invasive mold infection (aspergillosis, fusariosis, or zygomycosis), including pulmonary or hepatic nodules consistent with invasive mold infection for which patients are receiving targeted prophylaxis with amphotericin or other mold-active products
• No pre-transplantation-CMV disease (gastrointestinal or pneumonia)

PATIENT CHARACTERISTICS:

• Age
• 12 and over
• Performance status
• Not specified
• Life expectancy
• Not specified
• Hematopoietic
• Not specified
• Hepatic
• Not specified
• Renal
• Not specified
• Other
• HIV negative
• No hypersensitivity to acyclovir or valacyclovir
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• See Disease Characteristics
• Chemotherapy
• See Disease Characteristics
• Endocrine therapy
• Not specified
• Radiotherapy
• See Disease Characteristics
• Surgery
• Not specified

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Fred Hutchinson Cancer Research Center

Overall Clinical Trial Officials and Contacts

Garrett Nichols, MD, MSC Study Chair Fred Hutchinson Cancer Research Center  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00045292

Study ID Number: CDR0000256871

ClinicalTrials.gov Identifier: NCT00045292

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database