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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00016068
First received: May 6, 2001
Last updated: May 14, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention Phase
Infection
Drug: ganciclovir
Drug: valganciclovir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Supportive Care
Official Title: A Phase III Multicenter Study Of Valganciclovir For The Prevention Of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Late cytomegalovirus infection by plasma PCR positivity

Estimated Enrollment: 184
Study Start Date: January 2001
Study Completion Date: September 2007
Detailed 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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016068

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Michael Boeckh, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00016068     History of Changes
Other Study ID Numbers: 1577.00, FHCRC-1577.00, MSKCC-01127, NCI-H01-0072
Study First Received: May 6, 2001
Last Updated: May 14, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Fred Hutchinson Cancer Research Center:
infection

Additional relevant MeSH terms:
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Ganciclovir
Valganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014