Evaluation of Antifungal Prophylaxis on Graft-versus-host Disease (GVHD) Patients (ITRAG)
Evaluation of Antifungal Prophylaxis Against Invasive Fungal Infections During Corticosteroid Containing Therapy for Graft-versus-host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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 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.
Type d'étude
Inscription (Réel)
Phase
- Phase 4
Contacts et emplacements
Lieux d'étude
-
-
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Incheon, Corée, République de
- Inha University Hospital
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Incheon, Corée, République de
- Gachon University Gil Hospital
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Pusan, Corée, République de
- Inje University Pusan Paik Hospital
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Seoul, Corée, République de
- Seoul National University Hospital
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Seoul, Corée, République de, 135-710
- Samsung Medical Center
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Seoul, Corée, République de
- Chung-Ang University Hospital
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Seoul, Corée, République de
- Soonchunhyang University Seoul Hospital
-
-
Jeollanam-do
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Hwasun, Jeollanam-do, Corée, République de
- Chonnam National University Hwasun Hospital
-
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Kyounggi-do
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Bucheon, Kyounggi-do, Corée, République de
- Soonchunhyang University Bucheon Hospital
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
Patients developing or developed acute or chronic GVHD within the last 10 days which require systemic immunosuppressive therapy of corticosteroids with- or-without other immunosuppressive agents including calcineurin inhibitors.
- acute GVHD, grade 2-4
- chronic GVHD, mild grade with high risk or moderate to severe grade
- Written informed consent form
Exclusion Criteria:
- Aspartate transaminase or alanine transaminase level > 10 times UNL or Bilirubin or alkaline phosphatase level > 5 times UNL
- Active or chronic hepatitis virus B or C infection requiring antiviral therapy
- Estimated life expectancy < 30 days
- History of allergy, sensitivity, or any serious reaction to itraconazole oral solution
- Previous history of Zygomycosis
- Evidence of active fungal disease including high galactomannan titer above 0.5, within 2 weeks.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: itraconazole, prophylaxis, Oral solution
For GVHD patients who are required systemic glucocorticoids therapy, itraconazole oral solution will be administered at a dose of 200mg every 12 hours.
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200mg bid, oral solution, until a dose of prednisone was tapered to 10mg/day in case of prednisone alone therapy group, or until prednisone was stopped in case of CNIs plus prednisone, CNIs plus prednisone plus mycophenolate mofetil, or mycophenolate mofetil plus prednisone group, etc.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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incidence of proven or probable invasive fungal infections
Délai: at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
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at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
|
safety profiles of itraconazole oral solution
Délai: during GVHD treatment with corticosteroids containing regimen
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during GVHD treatment with corticosteroids containing regimen
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GVHD-specific survival (GSS) of patients receiving corticosteroids based GVHD treatment together with antifungal prophylaxis with itraconazole oral solution
Délai: from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications
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from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Dong Hwan Kim, M.D./Ph.D., Division of Hematology/Oncology, Department of Medicine
Publications et liens utiles
Publications générales
- Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008 Feb 1;46(3):327-60. doi: 10.1086/525258. No abstract available.
- Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea TC, Stiff P, Friedman DJ, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992 Mar 26;326(13):845-51. doi: 10.1056/NEJM199203263261301.
- Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL, Leitz GJ, Territo MC. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med. 2003 May 6;138(9):705-13. doi: 10.7326/0003-4819-138-9-200305060-00006.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Infections
- Maladies du système immunitaire
- Infections bactériennes et mycoses
- Mycoses
- Infections fongiques invasives
- Maladie du greffon contre l'hôte
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Inhibiteurs d'enzymes
- Hormones, substituts hormonaux et antagonistes hormonaux
- Inhibiteurs du cytochrome P-450 CYP3A
- Inhibiteurs des enzymes du cytochrome P-450
- Antagonistes hormonaux
- Agents antifongiques
- Inhibiteurs de la synthèse des stéroïdes
- Inhibiteurs de la 14-alpha déméthylase
- Itraconazole
Autres numéros d'identification d'étude
- 2009-08-099
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
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