Brief Title
Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients
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
Brief Summary
To investigate the efficacy of posaconazole as prophylaxis antifungal agent in aplastic anemia / hypoplastic myelodysplastic syndrome (AA/hMDS) patients undergoing antithymocyte globulin (ATG) treatment
Detailed Description
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
the incidence of proven/probable/possible fungal infection
Secondary Outcome
overall survival
Condition
Aplastic Anemia
Intervention
Posaconazole
Study Arms / Comparison Groups
posaconazole prophylaxis group
Description: aplastic anemia / hypoplastic myelodysplastic syndrome patients undergoing antithymocyte globulin treatment and receiving posaconazole as prophylaxis antifungal agent
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
40
Start Date
April 20, 2018
Completion Date
June 30, 2020
Primary Completion Date
June 30, 2019
Eligibility Criteria
Inclusion Criteria: 1. willing and able to provide written informed consent for voluntary participation in the trial 2. adult patients (≥18 years, <75 years old) 3. no QTc prolongation on initial ECG 4. Adequate organ function for treatment as follows: A. Absolute neutrophil count > 1.5 x 109/L B. Platelets >100 x 109/L C. Serum creatinine ≤ 2.0 x ULN (upper limit of normal) D. Serum bilirubin ≤ 1.5 x ULN E. AST and ALT ≤ 2.0 x ULN Exclusion Criteria: 1. those suspected of fungal infection within 30 days of ATG treatment 2. those allergic to -triazoles 3. those with history of malignancies within 5 years and/or concomitant malignancy other than AA/hMDS 4. those with history of chemotherapy, radiotherapy and/or other immunosuppressants 5. female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control 6. active HBV, HCV patients 7. HIV positive patients 8. those with history of receiving organ transplantation
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
, +82-10-9117-5012, [email protected]
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT03318159
Organization ID
H-1706-207-866
Responsible Party
Principal Investigator
Study Sponsor
Seoul National University Hospital
Collaborators
Merck Sharp & Dohme LLC
Study Sponsor
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Verification Date
April 2018