Evaluation of Antifungal Prophylaxis Against Invasive Fungal Infections During Corticosteroid Containing Therapy for Graft-versus-host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
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
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 steroid refractory GVHD (in this situation, investigator could stop
itraconazole oral solution if there is a potential drug interaction between itraconazole
oral solution and 2nd line GVHD drug or prolonged use of itraconazole oral solution could be
hazardous to the patient), 4) Need to switch antifungal agent for the treatment of prolonged
febrile episode related to systemic infection, thus requiring systemic antifungal treatment,
6) Withdrawal from study participation (patient's decision), or 7) Death.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
incidence of proven or probable invasive fungal infections
at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
Dong Hwan Kim, M.D./Ph.D.
Division of Hematology/Oncology, Department of Medicine
Korea: Food and Drug Administration