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

Mycoses Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01232504
• Other study ID #: L-09-01
• Status: Completed
• Phase: Phase 4
• First received: October 25, 2010
• Last updated: October 27, 2014
• Start date: September 2009
• Est. completion date: June 2013

Study information

• Verified date: October 2014
• Source: Xiamen Amoytop Biotech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: June 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Mycoses

Intervention

Drug:
• rhGM-CSF group
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).
• rhG-CSF+rhGM-CSF group
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).
• rhG-CSF group
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).

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Shanghai First People's Hospital	Shanghai	Shanghai
China	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Wuhan Tongji Hospital	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Xiamen Amoytop Biotech Co., Ltd.	Shanghai Jiao Tong University Affiliated First People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Hematological Engraftment	The median time of neutrophil and platelet recovery .	100 days post transplant	No
Secondary	Transplant Related Mortality	Transplant related mortality within 100 days after Allogeneic Stem Cell Transplantation (Allo-HSCT).	100 days post transplant	No
Secondary	Incidence of ?- ? Acute Graft Versus Host Disease (aGVHD)	Incidence of ?- ?acute 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	No
Secondary	IFD Related Mortality	IFD-related mortalities after a median follow-up of 600 days.	3-1099 days	No
Secondary	Relapse Related Mortality	Relapse related mortality after a median follow-up of 600 days.	3~1099 days	No
Secondary	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	No
Secondary	Hemorrhage Related Mortality	Hemorrhage related mortality after a median follow-up of 600 days	3-1099 days	No
Secondary	Infection Related Mortality	Infection related mortality after a median follow-up of 600 days.	3~1099 days)	No