Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients

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 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

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

, , 

Verification Date

April 2018