Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03318159|
Recruitment Status : Not yet recruiting
First Posted : October 23, 2017
Last Update Posted : October 23, 2017
|Condition or disease||Intervention/treatment||Phase|
|Aplastic Anemia Myelodysplastic Syndromes Fungal Infection||Drug: Posaconazole||Phase 2|
With compromised bone marrow function, patients with aplastic anemia (AA) and/and hypoplastic myelodysplastic syndrome (hMDS) are at an increased risk of invasive fungal infection. Moreover, the use of antithyocyte globulin (ATG), a part of standard first line treatment for AA/hMDS, increases the risk of fungal infection due to its antilymophocytic effects. It has been reported that fungal infection occurs most often in the first few weeks after initiation of ATG treatment, and the reported incidence of fungal infection overall varies from 9~80% for AA/hMDS patients. Among them invasive fungal infection accounts for 6-20% depending on reports. Such being the case, antifungal prophylaxis is recommended for AA/hMDS patients undergoing ATG treatment. More specifically, the British Committee for Standards in Haematology (BCSH) recognized the threat of increased invasive fungal infections in AA patients, and stipulated the use of mould (aspergillus) active azole, "preferably itraconazole or posaconazole" as prophylaxis. Unfortunately however, though many centers have adopted their own practice schemes, and antifungals have been routinely administered in the context of investigational regimens, there is no consensus as to which antifungal agent should be used.
Considering Aspergillus sp has remained the most common fungal isolate in AA patients for the past 20 years, it is only rational that an antifungal agent with broad spectrum, covering both yeast and fungi, be used in this context. Posaconazole, a triazole antifungal agent, not only has a broad coverage spectrum but also associated with predictable and reliable systemic bioavailability. Also for patients, once daily dosage is both pragmatic and convenient. According to meta-analyses of prophylactic antifungal agents use (published in 2007), fluconazole diminished the risk of fungal related mortality compared to placebo (RR 0.49, 95% CI: 0.32-0.75, P=0.0009). More importantly, when compared to fluconazole, posaconazole prophylaxis yielded even lesser fungal related mortality and significantly decreased invasive fungal infection rate. Considering the fact that posaconazole is already being used for acute myeloid leukemia (AML) and myelodysplastic syndromes patients undergoing induction treatment, it is only natural that posaconazole be used for AA/hMDS patients, who are at higher risk of developing invasive fungal infection compared to AML.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
open label, single arm, phase 2, multicenter
*historical control will be used for comparison: historical control patients are defined as those diagnosed with AA/hMDS and underwent ATG treatment with either fluconazole or itraconazole prophylaxis.
|Masking:||None (Open Label)|
|Official Title:||Open Label, Phase II Study Investigating the Efficacy of Posaconazole as Prophylaxis Antifungal Agent in Aplastic Anemia / Hypoplastic Myelodysplastic Syndrome Patients Undergoing Antithymocyte Globulin Treatment|
|Anticipated Study Start Date :||December 1, 2017|
|Estimated Primary Completion Date :||June 30, 2019|
|Estimated Study Completion Date :||December 31, 2019|
posaconazole prophylaxis group
aplastic anemia / hypoplastic myelodysplastic syndrome patients undergoing antithymocyte globulin treatment and receiving posaconazole as prophylaxis antifungal agent
Dosing of posaconazole Posaconazole tablet 300 mg twice daily on day 1; Maintenance dose: 300 mg once daily on day 2 and thereafter. Treatment period: 4 weeks
*if posaconazole tablet intolerance: posaconazole suspension 200mg tid
- the incidence of proven/probable/possible fungal infection [ Time Frame: during 4 weeks of posaconazole prophylaxis (i.e. upto 4 weeks) ]Define Invasive fungal infections according to guidelines of the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Mycoses Study Group of the National Institute of Allergy and Infectious Diseases (Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2008;46:1813-1821.
- overall survival [ Time Frame: through study completion, an average of 18 months ]The overall survival (OS) curves will be estimated using the Kaplan-Meier method
- any incidence of proven/probable/possible fungal infection [ Time Frame: through study completion, an average of 18 months ]Define Invasive fungal infections according to guidelines of the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Mycoses Study Group of the National Institute of Allergy and Infectious Diseases (Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2008;46:1813-1821.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318159
|Contact: Youngil Koh, MDemail@example.com|
|Contact: Yeri Seo||+82-2-331-2221||Yefirstname.lastname@example.org|