Aplastic AnemiaPhase 2NCT03318159
Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients
A Phase 2 study testing Posaconazole in people with Aplastic Anemia and Myelodysplastic Syndromes, run by Seoul National University Hospital at 1 site in South Korea.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Aplastic Anemia, Myelodysplastic Syndromes, Fungal Infection
- What is being tested?
- Posaconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Korea
- Study dates
- 20 Apr 2018to 15 Jul 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- willing and able to provide written informed consent for voluntary participation in the trial
- adult patients (≥18 years, <75 years old)
- no QTc prolongation on initial ECG
- Adequate organ function for treatment as follows:
- 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
Who cannot join
- those suspected of fungal infection within 30 days of ATG treatment
- those allergic to -triazoles
- those with history of malignancies within 5 years and/or concomitant malignancy other than AA/hMDS
- those with history of chemotherapy, radiotherapy and/or other immunosuppressants
- 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
- active HBV, HCV patients
- HIV positive patients
- those with history of receiving organ transplantation
Trial locations and contacts
1 site in 1 country.
About this study
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
To investigate the efficacy of posaconazole as prophylaxis antifungal agent in aplastic anemia / hypoplastic myelodysplastic syndrome (AA/hMDS) patients undergoing antithymocyte globulin (ATG) treatment
Read the 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.
- Conditions
- Aplastic Anemia, Myelodysplastic Syndromes, Fungal Infection
- Being tested
- Posaconazole
- Medical subject headings
- Anemia, Aplastic, Myelodysplastic Syndromes, Mycoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PosaconazoleDrug
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
| Study group | Role | What they receive |
|---|---|---|
| posaconazole prophylaxis group | Other | aplastic anemia / hypoplastic myelodysplastic syndrome patients undergoing antithymocyte globulin treatment and receiving posaconazole as prophylaxis antifungal agent Receives: Drug: Posaconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
the Incidence of Proven/Probable/Possible Fungal Infection
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.
Measured: during 4 weeks of posaconazole prophylaxis (i.e. upto 4 weeks)
Secondary outcomes (2)
Overall Survival
The overall survival (OS) curves will be estimated using the Kaplan-Meier method
Measured: through study completion, an average of 18 months
Any Incidence of Proven/Probable/Possible Fungal Infection
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.
Measured: through study completion, an average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start20 Apr 2018
- Primary completion15 Jul 2023
- Study completion15 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, YOUNGIL KOH, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318159
- Sponsor's protocol ID
- H-1706-207-866
- Status last verified
- Nov 2024
- First submitted
- 10 Oct 2017
- Last updated
- 20 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03318159
- Acronym / sponsor ID
- H-1706-207-866
- Conditions
- Aplastic Anemia, Myelodysplastic Syndromes, Fungal Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 20 Apr 2018 (actual)
- Primary completion
- 15 Jul 2023 (actual)
- Study completion
- 15 Jul 2023 (actual)
- First posted
- 23 Oct 2017 (actual)
- Results
- Posted 20 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| posaconazole prophylaxis group | Other | Drug: Posaconazoleaplastic anemia / hypoplastic myelodysplastic syndrome patients undergoing antithymocyte globulin treatment and receiving posaconazole as prophylaxis antifungal agent |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- willing and able to provide written informed consent for voluntary participation in the trial
- adult patients (≥18 years, <75 years old)
- no QTc prolongation on initial ECG
- Adequate organ function for treatment as follows:
- 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
Key exclusion criteria (8 listed)
- those suspected of fungal infection within 30 days of ATG treatment
- those allergic to -triazoles
- those with history of malignancies within 5 years and/or concomitant malignancy other than AA/hMDS
- those with history of chemotherapy, radiotherapy and/or other immunosuppressants
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PosaconazoleDosing 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 | Drug | posaconazole prophylaxis group |
Primary outcome
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.
2 secondary outcomes
Overall Survival
Time frame: through study completion, an average of 18 months
Any Incidence of Proven/Probable/Possible Fungal Infection
Time frame: through study completion, an average of 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Posaconazole in people with Aplastic Anemia and Myelodysplastic Syndromes, run by Seoul National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the Incidence of Proven/Probable/Possible Fungal Infection (time frame: during 4 weeks of posaconazole prophylaxis (i.e. upto 4 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.