Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00016068
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : May 17, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE May 6, 2001
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date May 17, 2010
Study Start Date  ICMJE January 2001
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
Late cytomegalovirus infection by plasma PCR positivity
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Valganciclovir to Prevent Cytomegalovirus Infection in Patients Following Donor Stem Cell Transplantation
Official Title  ICMJE A Phase III Multicenter Study Of Valganciclovir For The Prevention Of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation
Brief 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Masking: Double
Primary Purpose: Supportive Care
Condition  ICMJE Infection
Intervention  ICMJE
  • Drug: ganciclovir
  • Drug: valganciclovir
Study Arms  ICMJE Not Provided
Publications * Boeckh M, Nichols WG, Chemaly RF, Papanicolaou GA, Wingard JR, Xie H, Syrjala KL, Flowers ME, Stevens-Ayers T, Jerome KR, Leisenring W. Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial. Ann Intern Med. 2015 Jan 6;162(1):1-10. doi: 10.7326/M13-2729.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
184
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 2007
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00016068
Other Study ID Numbers  ICMJE 1577.00
FHCRC-1577.00
MSKCC-01127
NCI-H01-0072
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Michael Boeckh, MD Fred Hutchinson Cancer Research Center
PRS Account Fred Hutchinson Cancer Research Center
Verification Date May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP