Antifugal Effect of Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF) in Patients Post Allo-HSCT

Study Overview
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Brief Summary
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We conducted a prospective, multicenter, open-label randomized trial to compare the antifungal effect of Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF), Recombinant Human Granulocyte Stimulating Factor (rhG-CSF) or a combination of rhGM-CSF and rhG-CSF for neutropenic patients undergoing allogeneic stem cell transplantation.

Detailed Description
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From Sept 2009 to Dec 2012, we recruited consecutive patients with hematological diseases undergoing allogeneic stem cell transplantation at 5 institutions in China. Recipients between ages of 14 to 60 years old were eligible. Eligible patients were randomized to receive once daily subcutaneous 5-7μg/kg/d GM-CSF (Molgramostim, TOPLEUCON®; Xiamen Amoytop Biotech Co., Ltd., China) (GM-CSF group), 5-7μg/kg/d G-CSF (G-CSF group), or a combination of 2-3μg/kg/d GM-CSF and 2-3μg/kg/d G-CSF each (G-CSF+GM-CSF group). Administration of CSFs was started on day 5 post-transplant and continued until recovery from neutropenia (absolute neutrophil count [ANC] > 1.5×10(9)/L for 2 consecutive days). If absolute neutrophil count (ANC) decreased to < 1.5×10(9)/L within 5 days after withdrawal of CSFs, the same CSF would be resumed until the absolute neutrophil count (ANC) reached 1.5×10(9)/L again. All patients received antimicrobial prophylaxis with oral levofloxacin 500 mg daily and antifungal prophylaxis with oral fluconazole 200 mg daily.

Official Title
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Effect of Granulocyte-macrophage Stimulating Factor on Prevention and Treatment of Invasive Fungal Diseases in the Recipients of Allogeneic Stem Cell Transplantation: A Prospective Multicenter Randomized Phase 4 Trial

Conditions
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Mycoses

Intervention / Treatment
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* Drug: rhGM-CSF group
* Drug: rhG-CSF+rhGM-CSF group
* Drug: rhG-CSF group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 14 60 years old Allogenic hematological stem cell transplantation(HSCT) patients. Cardiac ejection factor ≥ normal upper limit, Aspartate aminotransferase and/or Alanine aminotransferase < 2 upper limit of normal, and/or total bilirubin < 2.5 upper limit of normal, creatinine < upper limit of normal. Informed consent. Exclusion Criteria: Evidence of proven, probable or possible fungal infection at the time of enrollment. Patients were receiving anti-fungal treatment with proven SFI before transplantation. A history of hypersensitivity to G-CSF or GM-CSF.
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhGM-CSF group<br>subcutaneous 5-7μg/kg/d Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF) once daily | Drug: rhGM-CSF group<br>* subcutaneous rhGM-CSF 5-7μg/kg/d , started on day 5 post-transplant and continued until recovery from neutropenia (absolute neutrophil count [ANC] > 1.5×10(9)/L for 2 consecutive days).<br>* Other names: Granulocyte Macrophage Colony Stimulating Factor;|
| Active Comparator: rhG-CSF+rhGM-CSF group<br>a combination of 2-3μg/kg/d Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF) and 2-3μg/kg/d Recombinant Human Granulocyte Stimulating Factor (rhG-CSF) each | Drug: rhG-CSF+rhGM-CSF group<br>* a combination of 2-3μg/kg/d rhGM-CSF and 2-3μg/kg/d rhG-CSF each after transplantation, started on day 5 post-transplant and continued until recovery from neutropenia (absolute neutrophil count [ANC] > 1.5×10(9)/L for 2 consecutive days).<br>* Other names: Granulocyte Colony Stimulating Factor;|
| Active Comparator: rhG-CSF group<br>subcutaneous 5-7μg/kg/d Recombinant Human Granulocyte Stimulating Factor (rhG-CSF) once daily | Drug: rhG-CSF group<br>* subcutaneous rhGM-CSF 5-7μg/kg/d , started on day 5 post-transplant and continued until recovery from neutropenia (absolute neutrophil count [ANC] > 1.5×10(9)/L for 2 consecutive days).<br>* Other names: Topleucon®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidences of Invasive Fungal Diseases (IFD) | The incidence of proven and probable Invasive fungal diseases (IFD) within 100 days post transplantation | 100 day post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological Engraftment | The median time of neutrophil and platelet recovery . | 100 days post transplant | 
| Transplant Related Mortality | Transplant related mortality within 100 days after Allogeneic Stem Cell Transplantation (Allo-HSCT). | 100 days post transplant | 
| Incidence of Ⅱ- Ⅳ Acute Graft Versus Host Disease (aGVHD) | Incidence of Ⅱ- Ⅳacute graft versus host disease (aGVHD) within 100 days after allogeneic stem cell transplantation (Allo-HSCT).The severity of acute GVHD in the three main target organs (skin, liver, gastrointestinal tract) was assigned stage 1 to 4 based on accepted criteria (Consensus Conference on Acute GVHD Grading). | 100 days post transplant | 
| IFD Related Mortality | IFD-related mortalities after a median follow-up of 600 days. | 3-1099 days | 
| Relapse Related Mortality | Relapse related mortality after a median follow-up of 600 days. | 3～1099 days | 
| Graft Versus Host Disease (aGVHD) Related Mortality | Graft versus host disease (aGVHD) related mortality after a median follow-up of 600 days . | 3-1099 days | 
| Hemorrhage Related Mortality | Hemorrhage related mortality after a median follow-up of 600 days | 3-1099 days | 
| Infection Related Mortality | Infection related mortality after a median follow-up of 600 days. | 3～1099 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allo-HSCT, rhGM-CSF, Systemic fungal infection (SFI)