Early Diagnosis of Aspergillosis in Patients at High Risk of Fungal Infection Caused by Treatment for Hematologic Cancer or Other Disease

Leukemia Clinical Trial

Official title:

Early Diagnosis of Invasive Aspergillosis in a High Risk Group of Patients Using Serum and Bronchoalveolar Lavage Fluid Real Time PCR and Galactomannan ELISA

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00462657
• Other study ID #: CDR0000539539
• Secondary ID: BARTS-PECT2005EU
• Status: Recruiting
• Phase: N/A
• First received: April 18, 2007
• Last updated: August 23, 2013
• Start date: July 2005

Study information

• Verified date: September 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Studying ways to diagnose fungal infections early may help doctors plan the best treatment.

PURPOSE: This clinical trial is studying laboratory tests to see how well they find aspergillosis early in patients at high risk of fungal infection caused by treatment for hematologic cancer or other disease.

Description:

OBJECTIVES:

Primary

• Determine the test characteristics of galactomannan (GM) ELISA using serum and bronchoalveolar lavage fluid (BALF) collected from patients at high risk of invasive fungal infection.

• Determine the test characteristics of aspergillus PCR using blood and BALF samples collected from these patients.

• Evaluate the role of noninvasive exhaled breath condensate (EBC) in detecting invasive aspergillosis (IA).

• Determine whether repeated measures over time or a combination of markers improves the test characteristics.

• Establish cutoff points for the diagnosis of IA.

Secondary

• Determine the inflammatory marker and cytokine profile of EBC in fungal infection and after bone marrow transplantation as a marker of acute lung injury.

• Assess the role of bronchoscopy with bronchoalveolar lavage in identifying the causal pathogen early in the disease course of febrile neutropenic patients.

• Assess the role of GM ELISA in prognosis and response to treatment for IA.

• Assess the role of aspergillus PCR in prognosis and response to treatment for IA.

OUTLINE: This is a prospective study.

Patients are assessed for early diagnosis of invasive aspergillosis (IA) using serum and bronchoalveolar lavage fluid (BALF) evaluated by ELISA for galactomannan (GM) antigen and real time PCR for fungal DNA. Serum samples are collected at baseline and periodically during study, beginning with the onset of neutropenia and continuing until resolution of fever or recovery of neutrophil count. BALF samples are collected in patients with abnormal chest radiology evaluated by bronchoscopy and bronchoalveolar lavage. BALF is analyzed for GM antigen, fungal DNA, inflammatory markers, and cytokines.

Patients are also assessed using exhaled breath condensate (EBC) evaluated by GM ELISA and real time PCR. EBC is collected at baseline and periodically during study to detect GM antigen or fungal DNA and to measure markers of pulmonary inflammation and oxidative stress (e.g., pH, hydrogen peroxide, and leukotriene B4).

PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• At high risk for developing invasive aspergillosis (IA) due to any of the following risk factors:

• Diagnosis of acute myeloid leukemia, myelodysplastic syndromes, or acute lymphoblastic leukemia AND meets = 1 of the following criteria:

• Receiving intensive chemotherapy with expected duration of neutropenia (ANC < 500/mm³) of > 10 days

• Receiving high-dose steroids

• Concurrent treatment with allogeneic hematopoietic stem cell transplantation (HSCT)

• Requirement for high-dose steroids for graft-versus-host disease after HSCT

• History of probable or proven IA and receiving chemotherapy

• No preexisting chest disease

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Aspergillosis
• Graft Versus Host Disease
• Graft vs Host Disease
• Infection
• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia

Intervention

Genetic:
• polymerase chain reaction

Other:
• bronchoalveolar lavage

• immunoenzyme technique

• laboratory biomarker analysis

Procedure:
• bronchoscopy

• management of therapy complications

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England

Sponsors (1)

Lead Sponsor	Collaborator
St. Bartholomew's Hospital

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity and specificity of galactomannan (GM) ELISA and real time PCR in detecting invasive aspergillosis (IA)			No
Primary	Diagnostic value of IA screening by GM ELISA and real time PCR, in terms of positive and negative predicative values			No