Clinical Trial: Evaluation of Antifungal Prophylaxis on Graft-versus-host Disease (GVHD) Patients
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Evaluation of Antifungal Prophylaxis Against Invasive Fungal Infections During Corticosteroid Containing Therapy for Graft-versus-host Disease Following Allogeneic Hematop
Brief Summary: Antifungal prophylaxis should be used in patients being treated with glucocorticoids for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem-cell transplantation (HSCT). Although fluconazole has been widely used as an antifungal prophylactic agent after allogeneic HSCT, fluconazole prophlaxis only shows a limited protective role against IFIs, is not effective against invasive aspergillosis. In addition, NCCN guideline of the prevention and treatment of cancer-related infections recommends antifungal prophylaxis in patients with significant GVHD until resolution of GVHD using Posaconazole, Voriconazole, Echinocandin, or Amphotericin B. However, under the National Health Insurance System, none of the drug can be given prophylactically except itraconazole oral solution against IFIs. Itraconazole oral solution shows excellent bioavailability and good efficacy against aspergillus and fluconazole resistant candida infection.Based on these findings, we will perform prospective multicenter study evaluating the efficacy, safety and long-term outcomes of itraconazole oral solution prophylaxis against IFIs in patients treated with systemic corticosteroids for GVHD after allogeneic HSCT.
Detailed Summary:
Eligible patients who provided an informed consent form will be administered itraconazole oral solution (200mg bid initially, swash and swallow) in either an in patient or outpatient setting. Treatment can be initiated at the same time of or within 10 days after starting systemic immunosuppressive therapy.
Itraconazole oral solution dose can be adjusted according to the liver function test: 1) in case of - AST/ALT level 5-10 times UNL or bilirubin/ALP level 2-5 times UNL, itraconazole dose can be reduced to half (i.e. itraconazole 200mg po once daily or 100mg bid); 2) in case of - AST/ALT level > 10 times UNL or bilirubin/ALP level > 5 times UNL, itraconazole can be stopped.
GVHD treatment can be given per center's policy: With respect to acute GVHD, prednisone (1-2mg/Kg/day) oral or iv can be given on top of calcineurin inhibitor (CNI) GVHD prophylaxis. For chronic GVHD, various type of frontline regimen can be permitted including CNI+prednisone (PD), PD alone, CNI+PD+mycophenolate mofetil (MMF), or MMF+PD. Various dose of PD will be accepted if it is at least from 0.5mg/Kg/day. For example, at SMC, in case of mild grade cGVHD with high risk feature, or of moderate grade cGVHD, CNI plus PD, 0.5mg/kg/day can be given initially. In case of severe grade cGVHD, CNI plus PD, 1.0mg/Kg/day will be given.
Itraconazole will be maintained until PD is tapered to 10mg/day in case of PD alone therapy group, or until PD is stopped in case of CNI+PD or CNI+PD+MMF or MMF+PD group, etc. In addition, patients will receive itraconazole oral suspension until: 1) Development of proven or probable IFIs, 2) Severe toxicity (such as liver function abnormality - AST/ALT level > 10 times UNL or bilirubin/ALP level > 5 times UNL, 3) Worsening GVHD that requires second line therapy for st
Sponsor: Samsung Medical Center
Current Primary Outcome: incidence of proven or probable invasive fungal infections [ Time Frame: at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis. ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- safety profiles of itraconazole oral solution [ Time Frame: during GVHD treatment with corticosteroids containing regimen ]
- GVHD-specific survival (GSS) of patients receiving corticosteroids based GVHD treatment together with antifungal prophylaxis with itraconazole oral solution [ Time Frame: from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications ]
Original Secondary Outcome: Same as current
Information By: Samsung Medical Center
Dates:
Date Received: January 23, 2011
Date Started: December 2009
Date Completion:
Last Updated: January 24, 2011
Last Verified: January 2011
