Escalation Antifungal Prophylaxis for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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This is single arm study to evaluate an escalation anti-fungal prophylaxis protocol for patients undergoing allogeneic stem cell transplantation. For all patients without documented proven or probable invasive fungal disease (IFD), patients will receive fluconazole during the treatment in the laminar air flow units (LAF). After discharged from LAF units, patients will receive anti-mold prophylaxis in case of haplo-identical or HLA-matched unrelated donor transplantation to d+100 without active acute GVHD (aGVHD). In case of active aGVHD, the prophylaxis treatment will be extended until recovery of aGVHD and tapering of immunosuppression. In case of HLA-matched sibling donor, fluconazole will be continued to d+100 and anti-mold prophylaxis will be given in case of active aGVHD.

Detailed Description
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Based on CAESAR study, the IFD incidence increased significantly in patients with unrelated donor or hallo-donor HSCT after patients being discharged from LAF units. The overall incidence of IFD in patients with HLA-matched sibling donor remain low unless in patients with active aGVHD. In this single-arm prospective study, we plan to evaluate the feasibility and effect of an escalation anti-fungal prophylaxis protocol for patients undergoing allogeneic stem cell transplantation. For all patients without documented proven or probable invasive fungal disease (IFD), patients will receive fluconazole during the treatment in the laminar air flow units (LAF). After discharged from LAF units, patients will receive anti-mold prophylaxis in case of haplo-identical or HLA-matched unrelated donor transplantation to d+100 without active acute GVHD (aGVHD). In case of active aGVHD, the prophylaxis treatment will be extended until recovery of aGVHD and tapering of immunosuppression. In case of HLA-matched sibling donor, fluconazole will be continued to d+100 and anti-mold prophylaxis will be given in case of active aGVHD.

Official Title
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Feasibility and Outcome of Anti-fungal Prophylaxis With an Escalation Pattern for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Fungal Infection

Intervention / Treatment
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* Drug: Escalating prophylaxis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients undergo allogeneic HSCT Conditioning regimens: myelo-ablative, reduced toxicity No proven or probable IFD before HSCT No allergy to fluconazole, voriconazle and posaconazole Inform consent given Exclusion Criteria: Imparied liver function with (AST or ALT>3ULN, TBil >2ULN)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escalating prophylaxis<br>For all patients without documented proven or probable invasive fungal disease (IFD), patients will receive fluconazole during the treatment in the laminar air flow units (LAF). After discharged from LAF units, patients will receive anti-mold prophylaxis in case of haplo-identical or HLA-matched unrelated donor transplantation to d+100 without active acute GVHD (aGVHD). In case of active aGVHD, the prophylaxis treatment will be extended until recovery of aGVHD and tapering of immunosuppression. In case of HLA-matched sibling donor, fluconazole will be continued to d+100 and anti-mold prophylaxis will be given in case of active aGVHD. | Drug: Escalating prophylaxis<br>* For all patients without documented proven or probable invasive fungal disease (IFD), patients will receive fluconazole during the treatment in the laminar air flow units (LAF). After discharged from LAF units, patients will receive anti-mold prophylaxis in case of haplo-identical or HLA-matched unrelated donor transplantation to d+100 without active acute GVHD (aGVHD). In case of active aGVHD, the prophylaxis treatment will be extended until recovery of aGVHD and tapering of immunosuppression. In case of HLA-matched sibling donor, fluconazole will be continued to d+100 and anti-mold prophylaxis will be given in case of active aGVHD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of IFD | Proven and probable diagnosis of IFD | day 180 after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of IFD2 | Proven, probable and possible IFD | day 180 after transplantation | 
| Incidence of IFD associated mortality | Documentation of death due to proven, probable and possible IFD | day 180 after transplantation | 
| Incidence of nor-relapse mortality (NRM) | Documentation of death not due to disease relapse or progression | day 180 after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fungal infection, stem cell transplantation, prophylaxis